Endocrine Physiology Review

Neural, Endocrine, Neuroendocrine, Paracrine and Autocrine

Peptides, Amines and Steroids

A chemical that is produced by the body and has a specific regulatory effect on a target cell or organ

Synthesized in rough ER. Stored in intracellular vesicles. Generally water soluble and do not require carrier proteins. Receptors are on plasma membrane of target cells. MOA is via second messengers. Usually fast onset of action but short acting responses.

Synthesized from tyrosine. Catecholamines are water soluble but thyroid hormones are not and require carrier proteins.

Synthesized from cholesterol. Diffuse rapidly out of the cell once produced due to high lipid solubility. Generally require carrier proteins. Receptor location is intracellular. MOA is via altered gene expression. Usually slow onset of action but long lasting response.

Dopamine, T3, T4, Epinephrine and Norepinephrine

Aldosterone, Cortisol, Testosterone, Estrogens, Progesterone and Vitamin D

Occurs when a hormone or response to a hormone directly inhibits further secretion of that hormone

Hormone secretion from a primary target gland that is controlled by pituitary hormones, which are in turn controlled by hypothalamic factors

The effects of the hormone result in further hormone secretion

An excess or deficiency of secretion by the TARGET GLAND

An excess or deficiency of secretion by the PITUITARY GLAND

An excess or deficiency of secretion by the HYPOTHALAMUS

Can effect the concentration of protein bound hormones; In hypoalbuminic states such as liver failure of nephrotic syndrome, the proportion of free calcium increases

In the nucleus

Is formed from ATP by the enyme adenylyl cyclase. The activity of Adenylyl cyclase depends on whether G stimulatory or inhibitory subunits are activated. cAMP activates protein kinase A and is degraded by a phosphodiesterase enzyme.

Are produced by phospholipase C which is activated by a G protein subunit. IP3 causes the release of stored calcium in the cell and DAG in the presence of calcium activates protein kinase C

Directly initiate phosphorylation in the cell when occupied with thier hormone

Guanylyl cyclase activates when hormone binds and produces cGMP from GTP. cGMP is broken down by a phosphodiesterase enzyme.

Are actually hormones themselves that are derived from arachidonic acid. This group includes prostaglandins, prostacyclins, thromboxanes and leukotrienes

Phospholipase A2; Corticosteroids inhibit this enzyme

COX; NDAID's inhibit this enzyme

LOX

Hormone diffuses into the cytoplasm and binds to receptor. Receptors dimerize and bind to DNA at a steroid response element upstream from the gene site.

Epithelial cells from the oral cavity

1. Growth hormone
2. Thyroid stimulating hormone
3. Adrenocorticotropic hormone
4. Follicle stimulating hormone
5. Lutenizing hormone
6. Prolactin

TRH
CRH
GnRH
GHRH/Somatostatin

If constantly stimulated, hormone receptors will be downregulated. A clinical example would be giving an agonist in high doses; at first, there will be an excess of hormone production - but later the production would drop drastically due to receptor downregulation

1. Regulator of final body size - stimulation of linear growth occurs via insulin like growth factor I
2. Metabolic effects that oppose insulin - lipolysis in adipose tissue, reduced glucose uptake in muscle and gluconeogenesis in the liver

During the first 2 hours of deep sleep.
Acute stress also induces GH secretion.

Hypoglycemia via the GI hormone ghrelin

Starvation

1. GH inhibits its own secretion
2. IGF-1 inhibits GH secretion
3. IGF-1 inhibits GHRH secretion
4. IGF-1 stimulates somatostatin secretion

Congestive heart failure

1. ADH - supraoptic nucleus
2. Oxytocin - paraventricular nucleus

ADH secretion is most sensitive to altered extracellular osmolality, which is sensed by neuronal osmoreceptors. An increase in plasma osmolarity of just 1% is sufficient to increase ADH secretion and cause thirst and water retention at the kidney

A decrease in blood volume of more than 15% is a highly potent stimulus for ADH secretion and results in renal water conservation.
Increased blood volume stretches the heart atria, which suppresses ADH secretion .

Vasopressin

V1: causes vasocontriction in vascular smooth muscle
V2: causes water retention in the kidney

Stimulate uterine contractions, stimulate milk ejection and promote maternal behavior

Dilation of the cervix stimulates release of oxytocin. Oxytocin stimulates uterine contraction. Uterine contractions cause further cervical dilation which causes more oxytocin release. The cycle ends upon birth of the infant.

1. Induction of labor
2. Treatment of postpartum hemorrhage

1. Aldosterone - zona glomerulosa
2. Cortisol - zona fasciculata
3. DHEA - zona reticularis

1. Addition of OH groups by hydroxylases
2. C-C bond cleavage by desomolase
3. Oxidation/reduction by hydroxysteroid dehydrogenase

This is how it works

DHEA

DHEA

Aromatase

1. 20,22-desmolase
2. 11-hydroxylase
3. 18-hydroxylase
4. 18-HSD

5-a-reductase

This system uses the DAG/IP3 second messenger system for upregulation and the antagonistic effect of cGMP on cAMP for downregulation

StAR stands for steroidogenic acute regulatory protein.
It shuttles cholesterol in and out of the mitochondria.

Production of StAR protein

1. Acute: availability of cholesterol (enzyme or transport defect)
2. Transport by StAR (the rate limiting step in all steroid pathways!)
3. Chronic: synthesis of P450 enzymes
4. Second messenger pathways (have to be intact)

Transport of cholesterol in/out of the mitochondria by StAR protein

They all contain zinc-finger domains.

1. corticosteroid binding globulin (CBG or transcortin)
2. sex hormone binding protein (SHBP) or gonadal steroid binding globulin (GBG)
3. albumin (non-specific)

In the liver.
1. Reduce double bonds in rings
2. Reduce keto groups to -OH
3. Conjugate hydroxyl groups with:
(a) Sulfate groups: Donor PAPS
(b) Glucuronic acid groups: Donor UDP-Glucuronic acid

Glucuronic acid

FSH, LH, ACTH and TSH.
(B-Flat)

Prolactin and GH

1. Dopamine (prolactin inhibiting factor)
2. CRH (regulates ACTH and B-endorphin)
3. TRH (regulates TSH and prolactin)
4. GnRH (regulates LH and FSH)
5. GHRH (regulates GH)
6. Somatostatin (inhibits GH and TSH secretion)