Endo & Repro Physiology and Anatomy Flashcards
Synthesis of Thyroid Hormones
- Thyroglobulin is synthesized from tyrosine in the follicular cells and extruded into follicular lumen
- Na/I cotransport pumps I- into the thyroid cell (inhibited by thiocyanate and perchlorate ions)
- Peroxidase oxidizes I- to I2 (peroxidase inhibited by PTU and methimazole)
- Peroxidase organifies I2 with tyrosine residues of thyroglobulin to form MIT and DIT (Wolff-Chaikoff effect - inhibition of organification by high levels of I-)
- Peroxidase couples MIT and DIT to form T3 and T4
- TSH stimulation causes endocytosis of iodinated thyroglobulin from the follicular lumen, digestion of thyroglobulin by lysosomal enzymes, and release of T3 and T4 into the serum, bound to TBG
- Thyroid deoiodinase catalyzes leftover MIT/DIT to I2
- In peripheral tissues, T4 is converted to T3by **5-iodinase **(5-iodinase inhibited by PTU and propanolol)
Functions of thyroid hormones
- Bone growth - TH act synergistically with GH and somatomedins to promote bone formation; TH also stimulates bone maturation
- Brain maturation - mental retardation in hypothryoid fetuses
- Beta-adrenergic effects - upregulates B1-receptors of the heart (treat with propanolol)
- Basal metabolic rate increase via increased Na/K ATPase activity, leading to increased O2consumption, RR, and body T
- Increased glycogenolysis, gluconeogenesis, lipolysis (catabolic effects)
Functions of glucocorticoids
- Increase gluconeogenesis (increase protein catabolism in muscle, decrease glucose utilization in adipose tissue, increase lipolysis)
- Anti-inflammatory and anti-immune (induce synthesis of lipocortin, which inhibits phospholipase A2; inhibit production of IL-2; inhibit release of histamine/serotonin from mast cells and platelets; inhibit leukocyte adhesion resulting in neutrophilia)
- exogenous steroids can cause reactivation of TB and candidiasis due to blocked IL-2 production
- Maintain vascular responsiveness to catecholamines (upregulate a1 receptors on arterioles)
- Decreasee bone formation (block osteoblast activity)
Mechanism of insulin secretion
- Glucose enters the beta cells via Glut 2 receptors
- Glucose is oxidized to ATP, which closes the K channels and depolarizes the beta cell
- Depolarization opens Ca channels, which leads to the secretion of insulin
Similarly, sulonylureas (tobutamide, glyburide) stimulate insulin secretion by closing K channels in beta cells.
Effect of serum Mg+2 on PTH secretion
- Mild decreases in serum Mg stimulate PTH secretion
- Severe decreases in serum Mg inhibit PTH secretion and produce symptoms of hypoparathyroidism
Common causes of Mg deficiency: diarrhea, aminoglycosides, diuretics, alcohol abuse
Anatomy of adrenal cortex/medulla
Adrenal cortex (derived from mesoderm); “GFR corresponds to salt, sugar, and sex”:
- Zona Glomerulosa releases aldosterone in response to Renin-Angiotensin
- Zona Fasiculata releases cortisol and sex hormones in response to ACTH
- Zona Reticularis releases sex hormones in response to ACTH
Adrenal medulla (dervied from neural crest):
- Chromaffin cells release catecholamines in response to preganglionic sympathetic fibers
Stimulators of insulin release
- Hyperglycemia (via GLUT-2 transporters in beta-islet cells)
- GH (also causes insulin resistance)
- Beta-2 agonists
17a-hydroxylase deficiency
17a-hydroxylase normally converts pregnelone and progesterone (zona glomerulosa) to 17-hydroxypregnelone and 17-hydroxyprogesterone (zona fasciculata)
17a-hydroxylase deficiency results in increased mineralocorticoids and decreased cortisol and sex hormones
Labs: HTN, hypokalemia, decreased DHT
- XY presentation - pseudo-hermaphroditism (ambiguous genitalia, undescended testes)
- XX presentation - lack secondary sexual development
21-hydroxylase deficiency
21-hydroxylase normally converts progesterone and 17-hydroxyprogesterone to 11-deoxycorticosterone and 11-deoxycortisol, respectively.
Deficient 21-hydroxylase results in decreased mineralocorticoids and cortisol, and increased sex hormones
Labs: hypotension, hyperkalemia, increased renin activity, increased concentration of 17-hydroxyprogesterone
- Most common congenital adrenal hyperplasia
- Presents in infancy as salt-wasting or in childhood as precocious puberty (virilization in girls)
11b-hydroxylase
11b-hydroxylase normally converts 11-deoxycorticosterone and 11-deoxycortisol and corticosterone and cortisol.
Deficiency results in decreased aldosterone (but increased 11-deoxycorticosterone), decreased cortisol, and icnreased sex hormones
Labs: HTN (due to increased 11-deoxycorticosterone) with low renin levels
- Presents as virlization in girls
Hormones that use cAMP signaling pathway
“FLAT ChAMP”:
- FSH
- LH
- ACTH
- TSH
- CRH
- hCG
- ADH (V2-receptor)
- MSH
- PTH
Also calcitonin, GHRH, glucagon
Male hormone production
- Arcuate nuclei of hypothalamus secrete pulsatile GnRH, which stimulates AP to secrete LH and FSH
- LH promotes testosterone synthesis in Leydig cells by stimulating cholesterol desmolase
- Leydig cells lack 21b-hydroxylase and 11b-hydroxylase so they do not synthesize glucocorticoids or mineralocorticoids
- FSH promotes spermatogenesis in Sertoli cells, which also secrete inhibit (neg feedback on FSH)
Female hormone production
- Arcuate nuclei of hypothalamus secrete pulsatile GnRH, which stimulates AP to secrete LH and FSH
- LH promotes testosterone synthesis in Leydig cells
- Androstendione diffuses to nearby granulosa cells, which convert adrostenedione to testosterone (via 17b-hydroxysteroid dehydrogenase) and then to 17b-estrogen (via aromatase)
- FSH stimulates aromatase activity
Functions of estrogen
- Maturation and maintenance of fallopian tubes, uterus, cervix, and vagina; endometrial proliferation
- Development of female secondary sex characteristics at puberty
- Breast development
- Upregulation of estrogen, LH, and progesterone receptors
- Proliferation and development of ovarian granulosa cells
- Maintains pregnancy, but lowers uterine threshold to contractile stimuli during pregnancy
- Stimulates prolactin secretion (but blocks its action on the breast)
- Inhibits LH/FSH secretion, except during ovulation
- Increases HDL, decreases LDL
Functions of progesterone
- Stimulation of endometrial glandular secretions and spiral artery development
- Maintains pregnancy and raises uterine threshold to contractile stimule during pregnancy
- Produces thick cervical mucus (inhibits sperm entry)
- Breast development
- Suppresses LH/FSH secretion
