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192 Cards in this Set
- Front
- Back
1. Psychosexual (definition)
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Term used to describe personality development and function as these are affected by sexuality.
Applies to more than sexual feelings and behavior and is NOT synonymous with libido |
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2. Sexuality depends of what four interrelated psychosexual factors?
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1. Sexual identity
2. Gender identity 3. Sexual orientation 4. Sexual behavior |
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3. Sexual identity and gender identity (definition)
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Sexual identity is the pattern of a person's biological sexual characteristics: chromosomes, external and internal genitalia, hormonal composition, gonads, and secondary sex characteristics
Gender identity is a person's sense of maleness or femaleness. Sexual identity and gender identity are interactive. |
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4. When does differentiation of the male from the female take place?
What occurs then? |
About the sixth week of embryonic life and is completed around the end of the third month.
Results from the action of fetal androgens |
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5. Important genes development
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Testes develop as a results of the Y chromosome which codes for the SRY gene.
SRY SOX9 DAX1 - plays a part in both sexes WNT4 - needed for Mullerian ducts |
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6. By what age do most people have a firm gender identity?
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By 2 to 3 years
Yet, even if maleness and femaleness develop normally, persons must still develop a sense of masculinity or femininity. |
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7. Where does the formation of gender identity come from?
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The formation of gender identity arises from parental and cultural attitudes, the infant's external genitalia, and a genetic influence, which is physiologically active by the sixth week of fetal life
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8. Virilizing adrenal hyperplasia (adrenogenital syndrome)
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Results from excess androgens in fetus with XX genotype
Most common female intersex disorder Associated w/enlarged clitoris, fused labia, hirsutism in adolescence |
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9. Turner's syndrome
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Results form absence of second female sex chromosome XO
Associated w/webbed neck, dwarfism, cubitus valgus, no sex hormones produces, and infertility |
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10. Klinefelter's syndrome
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Genotype is XXY
Male habitus present w/small penis and rudimentary testes b/c of low androgen production Weak libido; usually assigned as male. |
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11. Androgen insensitivity syndrome
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Congenital X-linked recessive disorder that results in inability of tissues to respond to androgens.
External genitals look female and crytorchid testes present. In extreme form the patient has breasts, normal external genitals, short blind vagina and absence of pubic and axillary hair. |
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12. Enzymatic defects in XY genotype
5-α--reductase deficiency 17-hydroxy-steroid deficiency |
Congenital interruption in production of testosterone that produces ambiguous genitals and female habitus
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13. True hermaphroditism
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True hermaphrodite is rare and characterized by both testes and ovaries in same person (may be 46 XX or 46 XY)
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14. Pseudohermpahroditism
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Usually the result of endocrine or enzymatic defect (CAH) in persons with normal chromosomes
Female pseudohermaphrodites have masculine looking genitals but are XX Male pseudohermaphrodites have rudimentary testes and external genitalia and are XY |
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15. Things needed to establish gender role
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The major factor in achieving the role appropriate to a person's sex is learning.
1. Experiences encountered 2. Explicit instruction 3. Spontaneously putting 2 and 2 together to make 4 and sometimes 5 4. Congruence of gender identity and gender role |
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16. Can a person's gender role be opposed to their gender identity?
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Yes, they may identify w/their own sex and yet adopt the dress, hairstyle or other characteristics of the opposite sex.
Or, they may identify with the opposite sex and yet for expediency adopt many behavioral characteristics of their own sex. |
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17. Role of the cortex in sexual behavior
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Involved in both controlling sexual impulses and in processing sexual stimuli that may lead to sexual activity
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18. Orbitofrontal cortex
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Involved in emotions
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19. Left anterior cingulate cortex
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Involved in hormone control and sexual arousal
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20. Right caudate nucleus
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Activity is a factor in where sexual activity follows arousal
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21. Role of limbic system in sexual behavior
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Directly involved w/elements of sexual functioning.
Chemical or electrical stimulation of the lower part of the septum and the contiguous preoptic area, the fimbria of the hippocampus, the mammilary bodies, and the anterior thalamic nuclei have all elicited penile erections.. |
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22. Role of brainstem in sexual behavior
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Exerts inhibitory and excitatory control over spinal sexual reflexes.
The nucleus paragigantocellularis projects directly to pelvic efferent neurons, apparently causing them to secrete serotonin, which is known to inhibit orgasm. |
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23. Roles of brain neurotransmitters in sexual behavior
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Dopamine increases libido
Serotonin, produced in the upper pons and midbrain, exerts an inhibitory effect on sexual function Oxytocin is released w/orgasm and is believe to reinforce pleasurable activities |
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24. Role of the spinal cord in sexual behavior
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Sexual arousal and climax are organized at the spinal level.
Sensory stimuli related to sexual functions are conveyed via afferents from the pudendal, pelvic, and hypogastric nerves. Proposed that sexual reflexes are mediated by spinal neurons in the central gray region of the lumbosacral segments. |
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25. What are the four phases of the sexual response cycle according to the DSM?
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1. Desire
2. Excitement 3. Orgasm 4. Resolution *It is important to remember that the sequence of responses can overlap and fluctuate. |
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26. Orgasm similarities and differences in males and females
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The male orgasm is also associated with four to five rhythmic spasms of the prostate, seminal vesicles, vas, and urethra.
In women, orgasm is characterized by 3 to 15 involuntary contractions of the lower third of the vagina and by strong sustained contractions of the uterus, flowing from the fundus downward to the cervix. Both men and women have involuntary contractions of the internal and external anal sphincters. These and the other contractions during orgasm occur at 0.8-second intervals. |
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27. Did Freud consider homosexuality a mental illness?
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No, he wrote that homosexuality is found in persons who exhibit no other serious deviations from normal whose efficiency is unimpaired and who are indeed distinguished by especially high intellectual development and ethical culture
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28. Circulatory androgens in gay men vs. heterosexual men
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Gay men exhibit lower levels of circulatory androgens than do heterosexual men
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29. Hyperadrenocorticalism
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Women with hyperadrenocorticalism are lesbian and bisexual in greater proportion than women in the general population.
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30. Genetic differences between gays and straights
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Genetic studies have shown a higher incidence of homosexual concordance among monozygotic twins than among dizygotic twins; these results suggest a genetic predisposition, but chromosome studies have been unable to differentiate homosexuals from heterosexuals.
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31. Ego-dystonic sexual orientation
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Occurs when the gender identity or sexual preference is not in doubt but the individual wishes it were different b/c of associated psychological and behavioral disorders and may seek treatment in order to change it.
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32. Endocrine hormones
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released by glands or specialized cells into the circulating blood and influence the function of cells at another location in the body.
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33. Neuroendocrine hormones
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Secreted by neurons into the circulating blood and influence the function of cells at another location of the body
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34. Paracrines
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Secreted by cells into the extracellular fluid and affect neighboring cells of a different type
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35. Autocrines
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Secreted by cells into the extracellular fluid and affect the function of the same cells that produced them by binding to cell surface receptors
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36. Cytokines
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Peptides secreted by cells into the extracellular fluid and can function as autocrines, paracrines, or endocrine hormones.
Include interleukins and lymphokines that are secreted by helper cells and act on other cells of the immune system. |
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37. Three classes of hormones
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1. Proteins and polypeptides
2. Steroids 3. Derivatives of the amino acid tyrosine |
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38. Where are polypeptide and protein hormones synthesized?
Where are they stored? |
Synthesized on the rER into preprohormones and then cleaved into prohormones in the ER. Then, they are transferred to the Golgi for packaging.
Enzymes in the vesicles cleave the prohormones to produce smaller, biologically active hormones. They are then stored in secretory vesicles until needed. |
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39. Polypeptides
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Those with 100 or more amino acids are called proteins
Those with fewer than 100 are called peptides |
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40. Secretion of hormones
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Occurs following the depolarization of the plasma membrane; the secretory vesicles fuse w/the cell membrane and the granular contents are extruded into the interstitial fluid or blood via exocytosis.
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41. Are peptide hormones water soluble?
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Yes, allowing them to enter the circulatory system easily to reach their target tissues.
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42. Synthesis and storage of steroid hormones
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Usually synthesized from cholesterol and are not stored. They are lipid soluble and consist of three cyclohexyl rings and one cyclopentyl ring combined into a single structure
Once they are synthesized, they simply diffuse across the cell membrane and enter the interstitial fluid and then the blood |
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43. What are the two groups of hormones derived from tyrosine?
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1. Thyroid hormones
2. Adrenal medullary hormones |
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44. Where are amine hormones derived from?
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Derived from tyrosine; formed by the actions of enzymes in the cytoplasmic compartments of the glandular cells.
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45. Thyroid hormones
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Synthesized and stored in the thyroid gland and incorporated into macromolecules of the protein thyroglobulin, which is stored in large follicles within the thyroid.
Hormone secretion occurs when the amines are split from thyroglobulin and the free hormones are then released into the blood stream. After entering the blood, they combine with plasma proteins, esp thyroxine-binding globulin, which slowly releases the hormones to the target tissues. |
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45. Epinephrine and norepinephrine
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Catecholamines:
Formed in the adrenal medulla, which normally secretes about 4x more epinephrine than norepinephrine. Taken up into preformed vesicles and stored until secreted. Also released from adrenal medullary cells by exocytosis. |
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46. Control variable in negative feedback of hormone systems
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It is not the secretory rate of the hormone itself, but rather the degree of activity of the target tissue.
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47. Example of positive feedback in hormones
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Luteinizing hormone:
Surge of LH occurs as a result of the stimulatory effect of estrogen on the anterior pituitary before ovulation. The secreted LH then acts on the ovaires to stimulate additional release of estrogen, which causes more LH to be screted. |
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48. Cyclical variations of hormone release
and example? |
Periodic variations of hormone secretion that are influenced by seasonal changes, various stages of development and aging, the diurnal cycle, and sleep.
Secretion of growth hormone is markedly increased during the early period of sleep but is reduced during the later stages of sleep. |
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49. Binding of hormones to plasma proteins
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Plasma bound hormones cannot easily diffuse across the capillaries and gain access to their target cells and are therefore biologically inactive until they dissociate from the plasma proteins.
Being bound also slows their clearance from the plasma |
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50. Two factors that can increase or decrease the concentration of a hormone in the blood
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1. Rate of hormone secretion into the blood
2. Rate of removal of the hormone from the blood (metabolic clearance rate) |
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51. Metabolic clearance rate
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Depends on:
D. the rate of disappearance of the hormone from the plasma per min C. the concentration of the hormone in each mL of plasma. MCR = D/C |
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52. How are hormones cleared from the plasma?
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1. metabolic destruction by the tissues
2. binding with the tissues 3. excretion by the liver into the bile 4. excretion by the kidneys into the urine |
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53. Location for the different types of hormone receptors are where?
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1. In or on the surface of the cell membrane
-mostly for the protein, peptide, and catecholamine hormone receptors 2. In the cell cytoplasm -primarily for steroid hormone receptors 3. In the cell nucleus -receptors for the thyroid hormones are found here |
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54. Down regulation of hormone receptors
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Increased hormone concentration and increased binding w/its target cell receptors sometimes cause the number of active receptors to decrease
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55. When does this down regulation occur?
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1. inactivation of some of the receptor molecules
2. inactivation of some of the intracellular protein signaling molecules 3. temporary sequestration of the receptor to the inside of the cell away from the hormones 4. destruction of the receptors by lysosomes after they are internalized 5. decreased production of the receptors |
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56. Up regulation of hormone receptors
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The stimulating hormone induces greater than normal formation of receptors or intracellular signaling molecules by the protein manufacturing machinery of the cell, or greater availability of the receptor for interaction w/the hormone.
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57. Ion channel-linked receptors
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When hormones bind with the receptors (usually neurotransmitters), they almost always cause a change in the structure of the receptor, usually opening or closing a channel for one or more ions.
Most hormones open or close these ion channels indirectly by coupling with G protein-linked or enzyme-linked receptors. |
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58. Protein-linked receptors
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Many hormones activate receptors that indirectly regulate the activity of target proteins by coupling w/groups of cell proteins called heterotrimeric GTP-binding proteins (G-proteins)
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59. G-proteins
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There are over 1000 known G proteins, all of which have 7 transmembrane segments that loop in and out of the cell membrane.
The three trimeric parts are alpha, beta, and gamma subunits. |
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60. Hormone action on G-proteins
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When the hormone binds to the G-protein, it causes a conformational change that causes the GDP-bound trimeric G-protein to associate w/the cytoplasmic part of the receptor and to exchange GDP for GTP.
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61. Significance of the exchange of GDP for GTP.
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This exchange causes the alpha subunit to dissociate from the trimeric complex and to associate with other intracellular signaling proteins, which, in turn alter the activity of ion channels or intracellular enzymes
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62. How does the G-protein deactivate itself?
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The signaling event is rapidly terminated when the hormone is removed and the alpha subunit inactivates itself by converting its bound GTP to GDP
Next, the alpha subunit once again combines w/the beta and gamma subunits to form the inactive G-protein |
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63. Inhibitory and stimulatory G proteins
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Some hormones couple to inhibitory or stimulatory G proteins.
Thus, depending on which they couple to, a hormone can either increase or decrease the activity of intracellular enzymes. |
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64. Enzyme-linked hormone receptors
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Some receptors when activated function directly as enzymes or are closely associate w/enzymes that they activate.
*They are proteins that pass thru the membrane only once. They have a hormone binding site on the outside of the cell and their catalytic or enzyme binding site is on the inside. |
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65. Example of an enzyme-lined receptor
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The leptin receptor; leptin is a hormone secreted by fat cells and has many physiological effects.
Binding of leptin to the extracellular part of the receptor alters its conformation and enables phosphorylation and activation of the intracellular associated JAK2 molecules. These JAK2 molecules then phosphorylate other tyrosine residues within the leptin receptor. |
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66. Catalytic formation of cAMP
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Another example of an enzyme-linked receptor; when the hormone binds with a special transmembrane receptor which then becomes the activated enzyme adenyl cyclase at the end that protrudes to the interior of the cell.
This cyclase catalyzes the formation of cAMP. |
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67. Intracellular hormone receptors
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Steroid hormones bind w/protein receptors on the inside of the cell b/c they are lipid soluble and can easily cross the cell membrane.
The activated hormone-receptor complex then binds w/a specific regulatory promoter sequence of the DNA called the "hormone response element" which either activates or represses gene transcription |
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68. Three important second messengers used by hormones
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1. cAMP
2. Calcium ions associated w/calmodulin 3. Products of membrane phospholipid breakdown |
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69. Release of cAMP
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Formed by stimulatory G-proteins on the inside of the cell and usually activates a cascade of enzymes.
The importance of this mechanism is that only a few mols of activated cAMP immediately inside the cell membrane can cause many more mols of the next enzyme to be activated, and so on. |
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70. Reduction of cAMP formation
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If the hormone receptor is coupled to an inhibitory G-protein, then adenyl cyclase will be inhibited, reducing the formation of cAMP.
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71. Action of cAMP in target cells
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Depends on the nature o the intracellular machinery.
Thus, a thyroid cell stimulated by cAMP forms thyroxine and T3, wheres the same cAMP in an adrenocortical cell causes secretion of the adrenocortical steroid hormones. |
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72. Cell membrane phospholipid second messenger system
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Some hormones activate transmembrane receptors that activate the enzyme phospholipase C.
This enzyme catalyzes the breakdown of some phospholipids in the cell membrane, which mobilizes calcium ions from mitochondria and ER and the calcium ions then have their own second messenger effects. |
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73. Arachidonic acid
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Precursor for the prostaglandins and other local hormones.
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74. Calcium-calmodulin second messenger system
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When Ca enters a cell, the ions bind w/the protein calmodulin.
This protein has four Ca sites, and when 3 or 4 of these sites have bound w/Ca, the calmodulin changes its shape and activates or inhibits protein kinases |
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75. Activation of calmodulin-dependent protein kinases
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Causes phosphorylation, activation or inhibition of proteins involved in the cells response to the hormone.
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76. Similarity of calmodulin system and skeletal muscle
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The calcium ion concentration needed to activate calmodulin is almost the same amount needed to activate troponin-C in skeleton muscle contraction
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77. Synthesis of proteins on target cells
Why is there a minimum 45 min delay for the full action of steroid hormones? |
1. The steroid hormone diffuses across the cell where it binds to the receptor protein
2. The combined receptor protein-hormone then diffuses into or is transported into the nucleus 3. The combination binds at specific points on the DNA strands in the chromosomes, which activates the transcription of mRNA 4. The mRNA diffuses into the cytoplasm where it promotes the translation process at the ribosomes to form new proteins |
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78. Type important features of thyroid hormones
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1. They activate the genetic mechanisms for the formation of many types of intracellular proteins
2. Once bound to the intranuclear receptors, the thyroid hormones can continue to express their control functions for days or even weeks |
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79. Radioimmunoassay 1
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A scientific method used to test antigens (for example, hormone levels in the blood)
To perform a radioimmunoassay, a known quantity of an antigen is made radioactive, frequently by labeling it with gamma-radioactive isotopes of iodine attached to tyrosine. This radiolabeled antigen is then mixed with a known amount of antibody for that antigen, and as a result, the two chemically bind to one another. Then, a sample of serum from a patient containing an unknown quantity of that same antigen is added. This causes the unlabeled (or "cold") antigen from the serum to compete with the radiolabeled antigen for antibody binding sites. |
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80. Radioimmunoassay 2
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As the concentration of "cold" antigen is increased, more of it binds to the antibody, displacing the radiolabeled variant, and reducing the ratio of antibody-bound radiolabeled antigen to free radiolabeled antigen.
The bound antigens are then separated from the unbound ones, and the radioactivity of the free antigen remaining in the supernatant is measured. A binding curve can then be plotted, and the exact amount of antigen in the patient's serum can be determined. |
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81. ELISA
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Enzyme-linked immunosorbent assay
is a biochemical technique used mainly in immunology to detect the presence of an antibody or an antigen in a sample. In simple terms, in ELISA an unknown amount of antigen is affixed to a surface, and then a specific antibody is washed over the surface so that it can bind to the antigen. This antibody is linked to an enzyme, and in the final step a substance is added that the enzyme can convert to some detectable signal. Thus in the case of fluorescence ELISA, when light of the appropriate wavelength is shone upon the sample, any antigen/antibody complexes will fluoresce so that the amount of antigen in the sample can be inferred through the magnitude of the fluorescence. |
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82. Why is the ELISA method widely used?
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1. It does not employ radioactive isotopes
2. Much of the assay can be automated using 96-well plates 3. It has proved to be a cost-effective and accurate method for assessing hormone levels. |
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83. Composition of the adrenal glands
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1. Adrenal medulla
-secretes epinephrine and norepinephrine 2. Adrenal cortex -secretes corticosteroids |
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84. Mineralcorticoids
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They specially affect the electrolytes (the "minerals") of the extracellular fluids; sodium and potassium, in particular.
Aldosterone: principal mineralcorticoid |
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85. Glucocorticoids
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They exhibit important effects that increase blood glucose concentration.
They have additional effects on both protein and fat metabolism that are equally as important to body function as their effects on carbohydrate metabolism. Cortisol: principal glucocorticoid |
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86. Three layers of the adrenal cortex
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1. zona glomerulosa
2. zona fasciculata 3. zona reticularis |
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87. Zona glomerulosa
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Outer layer:
Only layer with cells capable of secreting significant amts of aldosterone b/c they contain the enzyme aldosterone synthase. Secretion is controlled by angiotensin II and potassium. |
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88. Zona fasciculata
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Middle and widest layer:
Secretes glucocorticoids cortisol and corticosterone. Controleld in large part by the HPA axis via ACTH |
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89. Zona reticularis
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Deep layer:
Secretes the adrenal androgens DHEA and androstenedione. Also regulated by ACTH, although other factors such as cortical androgen-stimulating hormone from the pituitary may be involved. |
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90. Synthesis of adrenocortical hormones
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From cholesterol via de novo from small amounts of acetate, and 80% of the cholesterol used for steroid synthesis comes from LDL in the plasma
ACTH stimulates adrenal steroid synthesis but increasing the # of adrenocortical cell receptors for LDL Once cholesterol enters the cells, it is delivered to the mitochondria where it is cleaved by cholesterol desmolase to form pregnenolone. |
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91. Difference btwn cortisol and aldosterone
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Cortisol has a keto-oxygen on carbon 3 and is hydroxlated at carbon 11 and 21
Aldosterone has an oxygen atom bound at carbon 18 |
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92. Mineralocorticoids
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1. Aldosterone (very potent)
2. Desoxycorticosterone (1/30 as potent as aldosterone) 3. Corticosteone (slight mineralocorticoid activity) 4. 9α-Fluorocortisol (synthetic, slightly more potent than aldosterone) 5. Cortisol (very slight mineralocorticoid activity) 6. Cortisone (synthetic, slight mineralocorticoid activity) |
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93. Glucocorticoids
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1. Cortisol (very potent)
2. Corticosterone (way less potent than cortisol) 3. Cortisone (synthetic, almost as potent as cortisol) 4. Prednisone (synthetic, 5x as potent as cortisol 5. Dexamethasone (synthetic, 30x a potent as cortisol) |
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94. Metabolization of adrenocortical hormones
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Degraded mainly in the liver and conjugated especially to glucuronic acid and to a lesser extent, sulfates.
About 25% are excreted in the bile and then in the feces. |
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95. Function of aldosterone
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1. Increases renal tubular Excretion of potassium
2. Increases renal tubular Resorption of sodium and chloride 3. Maintenance of total extracellular fluid volume *Major mineralocorticoid secreted by the adrenals |
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96. Aldosterone and plasma sodium concentration
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Although it has a potent effect in decreasing the rate of sodium ion excretion by the kidneys, the concentration of sodium in the extracellular fluid often rises only a few milliequivalents.
This is b/c of the simultaneous osmotic resorption of water in the kidney tubules due to the increased sodium concentration. Also, small increases in sodium concentration stimulates thirst and increased water intake. Thus, the sodium concentration maintained |
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97. Aldosterone and arterial pressure
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An aldosterone mediated increase in extracellular fluid volume lasting more than 1-2 days leads to an increase in arterial pressure which increases kidney excretion of salt and water, called "pressure natriuresis" and "pressure diuresis", respectively.
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98. Aldosterone escape
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The return to normal of salt and water excretion by the kidneys as a result of pressure natriuresis and diuresis.
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99. Excess aldosterone
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1. Hypokalemia
2. Muscle weakness |
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100. Too little aldosterone
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1. Hyperkalemia
2. Cardiac toxicity |
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101. Hypokalemia
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When the potassium ion concentration falls below about 2 mEq/L and causes muscle weakness due to the alteration of the electrical excitability of the nerve and muscle fiber membranes which prevents the transmission of normal action potentials.
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102.Excess aldosterone can also cause
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A mild degree of alkalosis due to the increase in tubular hydrogen ion secretion
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103. Effect of aldosterone on sweat and salivary glands
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Both glands form a primary secretion that contains sodium chloride but much of the sodium chloride, on passing thru the excretory ducts, is reabsorbed, while potassium and bicarbonate ions are secreted.
Its effect on the sweat glands is important to conserve body salt in hot environments and the effect on the salivary glands is to conserve salt when excessive quantities of saliva are lost. |
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104. Sodium-potassium adenosine triphosphatase
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Aldosterone causes an increase in the enzyme sodium-potassium adenosine triphosphatase, which serves as the principal part of the pump for sodium and potassium exchange at the basolateral membranes of the tubular cells.
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105. Epithelial sodium channel proteins
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Inserted into the luminal membrane of th esame tubular cells that allows rapid diffusion of the sodium ions from the tubular lumen into the cell; then the sodium is pumped the rest of the way by the sodium-potassium pump.
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106. Evidence of nongenomic actions of aldosterone
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Aldosterone has been shown to increase formation of cAMP in vascular smooth muscle cells and in epithelial cells of the renal collecting tubules in less than two minutes.
This time period is far too short for gene transcription and translation of proteins. |
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107. Four factors that play an important role in the regulation of aldosterone
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1. Increased potassium ion concentration in the extracellular fluid increases aldosterone secretion
2. Increased activity of the renin-angiotensin system also increases aldosterone secretion 3. Increased sodium ion concentration in the extracellular fluid very slightly decreases aldosterone secretion 4. ACTH from the anterior pituitary gland is necessary for aldosterone secretion but has little effect in controlling the rate of secretion |
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108. Activation of the renin-angiotensin system
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Usually occurs in response to diminished blood flow to the kidneys or to sodium loss
Activation results in a severalfold increase in aldosterone secretion |
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109. Blocking the formation of angiotensin II
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Markedly decreases plasma aldosterone concentration without significantly changing cortisol concentration.
This demonstrates the important role of Ang II in stimulating aldosterone secretion during sodium depletion |
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110. Function of glucocorticoids
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Helps resist different types of physical or mental stress and minor illnesses.
At least 95% of the glucocorticoid activity of the adrenocortical secretions results from the secretion of cortisol, known also as hydocortisone. |
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111. Effects of cortisol on carbohydrate metabolism
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1. Stimulation of gluconeogenesis
2. Decreased glucose utilization by cells 3. Elevated blood glucose concentration |
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112. How does cortisol stimulate gluconeogenesis?
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1. Cortisol increases the enzymes required to convert amino acids into glucose in the liver cells.
2. Cortisol causes mobilization of amino acids from the extrahepatic tissues mainly from muscle. |
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113. How does cortisol decrease glucose utilization by cells?
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Most physiologist believe that glucocorticoids depress the oxidation of NADH to form NAD+. Because NADH must be oxidized to allow glycolysis, the effect could account for the diminished utilization of glucose by the cells.
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114. How does cortisol cause elevated blood glucose concentration?
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The increased rate of gluconeogenesis and reduction in the rate of the utilization of glucose by the cells causes the blood glucose to rise.
Sometimes this rise is occasionally great enough that the condition is called adrenal diabetes. -Insulin lowers the blood glucose concentration only a moderate amount in this case b/c the tissues are resistant to the effects of insulin (due to the glucocorticoids) |
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115. What are the effects of cortisol on protein metabolism?
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1. Reduction in cellular protein
2. Increases liver and plasma proteins 3. Increased blood AAs, diminishes transport of AAs into extrahepatic cells, and enhances transport into hepatic cells |
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116. Where is the exception to the reduction in cellular protein with cortisol?
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In the liver, which may cause:
1. increased rate of deamination fo AAs by the liver 2. increased protein synthesis in the liver 3. increased formation of plasma proteins by the liver 4. increased conversion of AAs to glucose (enhanced gluconeogenesis) |
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117. What are the effects of cortisol on fat metabolism?
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1. Mobilization of fatty acids from adipose tissue and enhances the oxidation of fatty acids in the cells
2. Obesity is caused by excess cortisol Essentially, the increased mobilization of fats helps shift the metabolic systems of cells to use fatty acids in times of starvation or other stresses instead of glucose |
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118. How is cortisol important in resisting stress and inflammation?
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Any stress increases ACTH secretion by anterior pituitary gland which causes cortisol secretion.
The rapid mobilization of AAs and fats make them immediately available for energy and for synthesis of other compounds needed by different tissues of the body. |
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119. What are the two main anti-inflammatory effects of cortisol?
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1. It can block the early stages of the inflammatory process before inflammation even begins
2. If inflammation has already begun, it causes rapid resolution of the inflammation and increased rapidity of healing. |
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120. How does cortisol prevent inflammation
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1. It stabilizes the lysosomal membranes which prevent lysosomes from rupturing
2. Decreases the permeability of the capillaries 3. Decreases both migration of white blood cells and phagocytosis 4. Suppresses the immune system, causing lymphocyte reproduction to decrease markedly 5. Attenuates fever mainly b/c it reduces the release of IL-1 from the white blood cells |
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121. How does cortisol resolve inflammation?
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It blocks most of the facts that promote inflammation and enhances the rate of healing due to the mobilization of AAs and uses these to repair the damaged tissue.
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122. What are some other effects of cortisol?
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1. Blocks the inflammatory response to allergic reactions
2. Decreases the number of eosinophils and lymphocytes in the blood 3. Large doses of cortisol causes atrophy of all the lymphoid tissue in the body 4. Increases red blood cell production |
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123. ACTH
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Controls secretion of cortisol.
Secreted by anterior pituitary gland It is a large polypeptide w/a chain length of 39 AAs |
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124. How is ACTH release controlled?
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The corticotropin-releasing factor (CRF) is secreted from the paraventricular nucleus of the hypothalamus and then carried to the anterior pituitary gland where it induces ACTH secretion.
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125. ACTH and second messengers
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Principal effect of ACTH on adrenocortical cells is the activation of adenylyl cyclas which induces formation of cAMP
Also causes activation of the enzyme protein kinase A, which causes the initial conversion of cholesterol to pregnenolone* *This is the rate limiting step for all the adrenocortical hormones |
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126. Where does cortisol have negative feedback inhibition?
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1. Hypothalamus to decrease the formation of CRF
2. Anterior pituitary gland to decrease the formation of ACTH *Stress can break through this negative feedback causing excessive cortisol secretion |
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127. Addison's disease
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Results from a failure of the adrenal cortices to produce adrenocortical hormones and this in turn is most freq caused by primary atrophy of the adrenal cortices
It causes: 1. Mineralocorticoid deficiency 2. Glucocorticoid deficiency 3. Melanin pigmentation 4. Possible "addisonian crisis |
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128. Symptoms of Addison's disease
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1. Progressive weakness and easy fatigability
2. GI disturbances 3. Loss of appetite 4. Weight loss 5. Hyperpigmentation of skin 6. Hyperkalemia 7. Hypernatremia 8. Volume depletion 9. Hypotension |
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129. Treatment of Addison's disease
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An untreated person w/total adrenal destruction dies w/in a few days to a few weeks due to weakness and circulatory shock.
Person can live for years if small quantities of mineralocorticoids and glucocorticoids are administered daily |
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130. Addisonian crisis
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In a person w/Addison's disease, the output of glucocorticoids does not increase during stress; this person is likely to have an acute need for excessive amounts of glucocorticoids to prevent death.
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131. Cushing's syndrome (Hyperadrenalism)
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Hypersecretion by the adrenal cortex due to:
1. Adenomas of the anterior pituitary gland that secretes large amount of ACTH which causes adrenal hyperplasia 2. Abnormal function of the hypothalamus that causes high levels of CRF which stimulates ACTH release 3. Ectopic secretion of ACTH by a tumor elsewhere in the body 4. Adenomas of the adrenal cortex |
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132. Characteristics of Cushing's syndrome
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1. Central obesity (about trunk and upper back)
2. Moon faces 3. Weakness and fatigability 4. Hirsutism 5. Hypertension 6. Plethora 7. Glucose intolerance/diabetes 8. Osteoporosis 9. Neuropsychiatric abnormalities 10. Menstrual abnormalities 11. Skin striae |
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133. Pituitary Cushing syndrome
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The most common form
ACTH levels are elevated and cannot be suppressed by the administration of low dose dexamethasone but the pituitary then responds to higher doses of injected dexamethasone |
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134. Ectopic ACTH Cushing syndrome
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Results in an elevated ACTH but its secretion is completely insensitive to low or high doses of dexamethasone
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135. Adrenal tumor Cushing syndrome
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The ACTH level is quite low b/c of feedback inhibition of the pituitary.
Both low and high does dexamethasone fail to suppress cortisol excretion |
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136. Cushing syndrome effects on carbohydrate and protein metabolism
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Abudance of cortisol can caused increased blood glucose concentration and high levels of glucocorticoids cause protein catabolism which results in severe weakenss.
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137. Treatment of Cushing syndrome
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Consists of removing an adrenal tumor if this is the cause or decreasing the secretion of ACTH if this is possible.
If ACTH secretion cannot easily be decreased, the only satisfactory treatment is usually bilateral partial or total adrenalectomy. |
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138. Conn's syndrome (Primary Aldosteronism)
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An autonomous overproduction of aldosterone, with resultant suppression of the renin-angiotensin system.
It results in: 1. Hypokalemia 2. Increase in extracellular fluid volume and blood volume 3. Almost always, hypertension 4. Occasional periods of paralysis caused by hypokalemia. |
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139. Causes of primary aldosteronism
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1. Adrenocortical neoplasm that produces large amounts of aldosterone
2. Primary adrenocortical hyperplasia 3. Glucocorticoid--remediable hyperaldosteronism which leads to a sustained production of hybrid steroids in addition to both cortisol and aldosterone. |
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140. Dx criteria of primary aldosteronism
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Decreased plasma renin concentration
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141. Treatment of primary aldosteronism
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Surgical removal of the tumor or most of the adrenal tissue when hyperplasia is the cause.
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142. Androgenital syndrome
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Due to an excessive quantity of androgens that cause intense masculinizing effects throughout the body.
The excretion of 17-ketosteroids in the urine are 10 to 15x normal which is the useful in the diagnosis of this disease. |
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143. Three distinctive hyperadrenal clinical syndromes
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1. Cushing syndrome
2. Hyperaldosteronism 3. Adrenogenital syndrome |
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144. Cortical carcinomas vs. adenomas or hyperplastic processes
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Cortical carcinomas tend to produce more marked hypercortisolism, are larger in size when compared to the adenomas or hyperplastic processes
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145. Where do a majority of hyperplastic adrenals arise from?
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From secondary influences; primary cortical hyperplasia is uncommon
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146. Congenital adrenal hyperplasia (CAH)
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Represents a group of autosoma-recessive, inherited metabolic errors, each characterized by a deficiency of total lack of a particular enzyme involved in the biosynthesis of cortical steroids, particularly cortisol.
Steroidogenesis is then channeled into other pathways, leading to increased production of androgens, which accounts for virilization. Also, the decrease in cortisol results in the increased secretion of ACTH, resulting in adrenal hyperplasia. |
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147. 21-Hydroxylase deficiency
What are the three distinctive syndromes associated w/this deficiency? |
Defective conversion of progesterone to 11-deoxycorticosterone by 21-hydroxylase (CYP21B) accounts for over 90% of cases of CAH.
May range from a total lack to a mile loss. Associated with: 1. Salt-wasting (classic) adrenogenitalism 2. Simple virilizing adrenogenitalism 3. Nonclassic adrenogenitalism |
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148. Mechanism of CYP21B gene inactivation
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Involved recombination w/a neighboring pseudogene on chromosome 6p21 called CYP21A.
In th emajority of cases of CAH, portions of the CYP21A pesudogene replace all or part of the active CYP21B gene. The intro of nonfunctional sequences from CYP21A into the CYP21B sequence has the same effect as inactivating mutations in CYP21B. |
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149. Salt-wasting (classic) adrenogenitalism
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Results from an inability to convert progesterone into deoxycorticosterone b/c of a total lack of the hydroxylase (21-Hydroxylase).
Thus, there is no synthesis of mineralocorticoids and deficient cortisol synthesis. Causes: 1. Salt wasting 2. Hypnatremia 3. Hyperkalemia 4. Acidosis 5. Hypotension 6. Cardiovascular collapse 7. *Virilization* |
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150. Male vs. female differences in virilization in Salt-wasting adrenogenitalism
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Females have a range of mild clitoral enlargement to complete labioscrotal fusion to marked clitoral enlargement enclosing the urethra, thus producing a phalloid organ
Males with this disorder are generally unrecognized at birth but come to clinical attention 5 to 15 days later b/c of some salt losing crisis. |
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151. Simple virilizing adrenogenitalism
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(Without salt wasting)
Presents w/genital ambiguity and may occur in individuals w/a less than total 21-Hydroxylase defect b/c the level of mineralocorticoids, although reduced, is sufficient for salt reabsorption. However, the lowered glucocorticoid level fails to cause feedback inhibition of ACTH secretion. Thus, testosterone is increased, and ACTH is elevated, with adrenal hyperplasia. |
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152. Nonclassic adrenogenitalism
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Much more common than the other syndromes; patients may be virtually asymptomatic or have mild manifestations, such as hirsutism.
Dx can be made only by demonstration of biosynthetic defects in steroidogenesis and by genetic studies. |
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153. Neonates w/ambiguous genitalia
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CAH should be suspected in any neonate w/ambiguous genitalia.
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154. Treatment of CAH
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Treated w/exogenous glucocorticoids, which in addition to providing adequate levels of glucocorticoids, also suppress ACTH levels and thus decrease the excessive synthesis of steroid hormons responsible for many clinical abnormalities.
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155. Three patterns of adrenocortical insufficiency
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1. Primary acute adrenocortical insufficiency (adrenal crisis)
2. Primary chronic adrenocortical insufficiency (Addison disease) 3. Secondary adrenocortical insufficiency |
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156. Primary acute adrenocortical insufficiency
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May be caused by either primary adrenal disease (primary hypoadrenalism) or decreased stimulation of the adrenals owing to a deficiency of ACTH (secondary hypoadrenalism)
Occurs in: 1. Adrenal crisis 2. Patients maintained on exogenous corticosteroids 3. Massive adrenal hemorrhage |
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157. Waterhouse-Friderichsen syndrome
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1. Overwhelming bacterial infection
2. Rapidly progressive hypotension leading to shock 3. Disseminated intravascular coagulation w/widespread purpura 4. Rapidly developing adrenocortical insufficiency associate w/massive bilateral adrenal hemorrhage The adrenals are converted to sacs of clotted blood virtually obscuring all underlying detail. |
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158. What are the four most common causes of primary adrenal insufficiency?
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1. Autoimmune adrenalitis
2. Tuberculosis 3. AIDS 4. Metastatic cancers |
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159. Primary chronic adrenocortical insufficiency
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Known as Addison disease; results from progressive destruction of the adrenal cortex.
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160. Secondary adrenocortical insuffiency
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Any disorder of the hypothalamus and pituitary that reduces the output of ACTH leads to a syndrome of hypodrenalism that has many similarities to Addison disease.
Prolonged administration of exogenous glucocorticoids suppresses the output of ACTH and adrenal function. With secondary disease, the hyperpigmentation of primary Addison disease is lacking because melanotropic hormone levels are low Also, the adrenals may be moderately to markedly reduced in size. |
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161. Adrenocortical adenomas
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Clinically silent and are usually encountered as incidental findings at times of autopsy or during abdominal imaging.
There are two types; functional and non-functional; Functional are associated w/atrophy of the adjacent cortex |
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162. Adrenocortical carcinomas
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Rare neoplasms that can occur at any age, including childhood
More likely to be functional than adenomas are, and carcinomas are therefore often associated w/virilism or hyperadrenalism. Invasion of contiguous structions, including the adrenal vein and IVC, is common. May be difficult to differentiate from carcinoma that metastatized to the adrenals. |
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163. Two inherited causes of adrenal cortical carcinomas
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1. Li-Fraumeni syndrome
2. Beckwith-Wiedemann syndrome |
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164. Adrenal cysts
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Relatively uncommon lesions.
They may produce an abdominal mass and flank pain. Both cortical and medullary neoplasms may undergo necrosis and cystic degeneration and may present as non-functional cysts. |
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165. Adrenal myelolipomas
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Unusual benign lesions composed of mature fat and hematopoietic cells.
May be seen in cortical tumors and in adrenals with cortical hyperplasia |
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166. What is the rate-limiting step in the synthesis of cortisol?
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The conversion of cholesterol to pregnenolone
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167. What oxidase enzyme catalyzes each step in the pathway of adrenocortical hormone synthesis?
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Mitochondrial cytochromes; similar to the liver P450 oxidase system.
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168. Why does the zona fasciculata synthesize cortisol, but not aldosterone or androgens?
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The enzymes required for cortisol synthesis, such as steroid 11β-hydroxylase, are expressed in the zona fasciculata, whereas enzymes required for aldosterone and androgen synthesis are not.
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169. What are the most important plasma proteins that binds cortisol?
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Corticosteroid-binding globulin (CBG) and albumin
CBG has a high affinity for cortisol but low overall capacity, whereas albumin has low cortisol affinity but high overall capacity |
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170. Where are the primary sites of peripheral cortisol metabolism?
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1. Liver
2. Kidneys |
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171. Type I vs. Type II glucocorticoid receptors
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Mineralocorticoid receptors
Expressed in the organs of excretion (kidney, colon, salivary glands, sweat glands) Type II receptors, on the other hand, have a broader tissue distribution |
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172. Regulation of cortisol production
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1. Neurons from the hypothalamus secrete CRH
2. CRH binds to the G-protein receptors on the anterior pituitary gland 3. CRH binding stimulates production of proopiomelanocortin (POMC) 4. Cleavage of POMC yields ACTH and melanocyte stimulating hormone (MSH) 5. ACTH promotes synthesis of cortisol 6. High cortisol levels decrease synthesis and release of CRH and ACTH |
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173. Why is tapering to a lower dosage of exogenous glucocorticoids necessary?
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If not tapered, can result in sondary adrenal insufficiency
Necessary to allow the HPA axis to regain full activity. Exogenous glucocorticoids cause atrophy of the adrenal cortex |
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174. Cortisol analogues
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1. Prednisone
2. Prednisolone 3. Fludrocortison 4. Dexamethasone |
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175. Glucocorticoid receptor agonists
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Mimic cortisol function by acting as agonists at the glucocorticoid receptor
1. Prednisone 2. Prednisolone 3. Methyprednisolone 4. Dexamethasone 5. Hydrocortisone 6. Fluticasone 7. Beclomethasone 8. Flunisolide 9. Triamcinolone 10. Budesonide |
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175. Clinical application of glucocorticoid receptor agonists
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1. Inflammatory conditions in many different organs
2. Autoimmune diseases 3. Replacement therapy for primary and secondary adrenal insufficiency |
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176. Adverse effects of glucocorticoid receptor agonists
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1. Immunosuppression
2. Hyperglycemia 3. Hypercortisolism 4. Impaired wound healing 5. Hypertension 6. Fluid retention 7. Inhaled oropharyngeal candidiasis |
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177. Contraindications of glucocorticoid receptor agonists
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Systemic fungal infection
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178. Inhaled glucocorticoids
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1. Fluticasone
2. Beclomethasone 3. Flunisolide 4. Triamcinolone 5. Budesonide *Inhaled formulations greatly reduce systemic adverse effects; do not switch abruptly from high-dose oral to inhaled glucocorticoids |
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179. Glucocorticoid receptor antagonists
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Competitive antagonist of cortisol action at the glucocorticoid receptor
Mifepristone (RU-486) |
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180. Clinical application of glucocorticoid receptor antagonists
Common adverse effects? |
Causes abortion (through day 49 of pregnancy)
Also, at high doses, it could potentially be useful in the treatment of ectopic ACTH syndrome Can result in prolonged bleeding time, bacterial infections, sepsis, nausea, vomiting, diarrhea, cramps, vaginal bleeding, headache |
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181. Contraindications of glucocorticoid receptor antagonists
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1. Chronic adrenal failure
2. Ectopic pregnancy 3. Hemorrhagic disorders 4. Anticoagulation theraphy 5. Intrauterine devices |
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182. Inhibitors of glucocorticoid synthesis
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Inhibits various steps in the glucocorticoid hormone biosynthesis
Includes: 1. Mitotane 2. Aminoglutethimide 3. Metyrapone 4. Trilostane 5. Ketoconazole |
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183. Mitotane
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Used in medical adrenalectomy in cases of severe Cushing syndrome or adrenocortical CA
Can cause visual disturbances, and hemorrhagic cystitis Also can cause hypercholesterolemia Contraindications is the Live rotavirus vaccine Structural analogue to DDT that is toxic to adrenocortical mitochondria |
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184. Aminoglutethimide
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Used to treat Cushing's syndrome
Can cause: Cortisol insufficiency, agranulocytosis, leukopenia, neutropenia, pancytopenia, pruritus, hypotension. Contraindicated in hypersensitivity to glutethimide or aminoglutethimide Inhibits side chain cleavage enzyme as well as aromatase, which is important for conversion of androgens to estrogens |
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185. Metyrapone
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Used for Dx evaluation of HPA axis and in Cushing's syndrome
Can cause cortisol insufficiency and hypertension Contraindicated with adrenal cortical insufficiency Inhibits 11β-hydroxylation, resulting in impaired cortisol synthesis Can also result in disinhibition of ACTH secretion |
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186. Trilostane
|
Used in Cushing's syndrome and aldosteronism
Can cause an Addisonian crisis, postural hypotension, hypoglycemia Contraindicated w/adrenal cortical insufficiency, and renal or hepatic dysfunction Reversible inhibitor of 3β-hydroxysteroid dehydrogenase, which reduces aldosterone and cortisol production in the adrenal cortex |
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187. Mineralocorticoid receptor agonists
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Agonist at the mineralocorticoid receptor
Fludrocortisone |
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188. Fludrocortisone
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Used in hypoaldosteronism
Can cause hypertension, hypokalemia, heart failure, thrombophlebitis, secondary hypocortisolism, edema, rash, hyperglycemia Contraindicated w/systemic fungal infection Adverse effects are related to its ability to mimic a state of mineralocorticoid excess |
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189. Mineralocorticoid receptor antagonists
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Competetive antagonist of aldosterone action at the mineralocorticoid receptor
Includes: 1. Spironolactone 2. Eplerenone |
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190. Adrenal sex steroid (DHEA)
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DHEA is a prohormone that is converted to testosterone in the periphery
Used in hypoaldosteronism and in chronic fatigue syndrome Can cause acne, hepatitis, hirsutism, androgenization Contraindicated w/breat, ovarian or prostate CA May be used as replacement therapy for cases of Addison's disease w/documented DHEA deficiency. |