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What are the pathways for steroidogenesis in the adrenal cortex?


There are 7 steps.

1) Circulating cholesterol is bound to LDLproteins and then bound to LDL receptors on cells of the adrenal cortex. Cholesterol is endocytosed and esterified for storing.
2) stored cholesterol is released by hydroxylation reaction and brought to outer membrane of mitochondria
3) cholesterol is transferred to inner mitochondrial membrane
4) cholesterol is converted into pregnenolone (Rate limiting) (Angiotensin II and ACTH speeds it up)
5) Pregnenolone is brought to ER
6) Pregnolone unders a series of enzymatic reactions (CYP17 or aldosterone synthase)
7) the end product is very hydrophobic and instantly secreted


What is the pathway of Growth Hormone release?


1) Stimulants:
will cause the hypothalamus to secrete GHRH (growth hormone releasing hormone)

2) GHRH (binds to receptors on the anterior pituitary)
OR: CNS triggers somatostatin release which also binds at the level of anterior pituitary.

  • at the level of somatostatin (alpha 2 is inhibitory, beta2 is stimulatory)
    3) the somatotropes will secrete growth hormone.
    4) growth hormone travels to liver and leads to production of IGF-1
    5) IGF and GH both have binding proteins. Which increase half life.
    6) IGF-1 has a negative feedback on Growth hormone.

Describe the entire pathway of TH and TSH.


The production of thyroid hormone:
1) iodine is brought into circulation through the Na/I symporter and thyroglobulin is synthesized in the ER and secreted into the lumen.

2) Iodine becomes activated through oxidation by the TPO enzyme.
3) Iodine is added to thyroglobulin by again the TPO enzyme. Then coupling by TPO.
4) It is stored in the lumen as colloid, until TSH….
5) Increased caloric intake, cold temperatures and leptin tell the hypothalamus to release TRH which tells the anterior pituitary to secrete TSH into blood stream,

6) TSH does several things, activates TPO, TG expression, Na/K Atpase expression for iodine influx, increased enzymatic rate of oxidation, iodination, and coupling, uptake and oxidation of glucose for NADPH and H2o2 production, stimulation of lysosome fusion, increasing size and number of follicular cells increasing thyroid gland vascularity, AND
- endocytosis of colloid

7) colloid droplets fuse with lysosomes (DIT and MIT) get recycled. The T3 and T4 don’t get recycled and released into general circulation.
8) 5’-deiodinase converts T4 to T3 or r-T3.
9) T4 binds to binding proteins with higher affinity than T3 so it has longer half life. TBG, transthyretin, albumin act as mobile reservoirs
10) T3 binds to the TR with higher affinity. Forming a heterodimer with RXR it will bind the thyroid hormone response elements which recruits co-activators leading to transcription of genes that ultimately increase BMR or bone/muscle growth in children.


Describe FgF23 regulation of elevated serum phosphate.


IN conditions of hyperphosphatemia, calcitriol and osteocytes will both lead to secretion of FGF23

FGF23 blocks vitD and PTH so there is no phosphate reabsorption. The PTH is included because it wants to be the sole regulator.

FGF23 is the housekeeper to preventing hyperphosphatemia.


What do sertoli cells secrete and what are the effects?


Sertoli cells secrete activin and inhibin, thereby regulating FSH secretion.
FSH from anterior pituitary will act on seminiferous tubules increasing spermatogenesis as well as increase sensitivity of Leydig cells to LH.

Sertoi cells also secrete AMH, ensuring male pattern of reproductive ducts as well as secrete testosterone which stops before birth and restarts are puberty.

Sertoli cells lastly secrete ABP which maintains high local concentrations of testosterone.


Describe the levels of FSH and LH during on 28 day cycle and what accounts for the levels


Generally throughout the follicular phase, LH and FSH are both low. Then there is a surge right before ovulation and they’re both still rather high but slowly decline (LH is always higher than FSH except at the very end of the cycle)

During the follicular phase, FSH is kept low for two reasons.

  1. The preovulatory follicle is producing inhibin B. Inhibin B inhibits FSH secretion thereby starving neighboring follicles and they undergo atresia
  2. There is low consistent levels of estrogen and this knocks out the GnRH pulse generator.

In the preovulatory phase: estrogen rises and there is a switch to positive feedback. FSH soars. The rising estrogen causes the gonadotropes to secrete activin. Activin also promotes FSH secretion and causes the remaining preovulatory follicle to become a corpus luteum due to FSH stimulating an increase in LH-R expression.

The later fall in FSH is due to corpus luteum secreting inhibin A. Inhibin A is stimulated by LH and the elevated progesterone and estradiol negatively feedback on FSH/LH. ((progesterone is a POTENT inhibitor of LH and source of progesterone is granulosa and theca lutein cells as well as placenta if pregnant.


Describe the levels of progesterone and estradiol during a cycle.


Overall estradiol is kept higher than progesterone but both are low throughout the follicular phase. Then there is a rise in estrogen with a small rise in progesterone in the preovulatory phase.

After ovulation there is a huge level of progesterone > estradiol throughout the luteal (peaks mid luteal) and falls, reaching about the same level as estradiol rigth at the end.
Progesterone is a thermogenic molecule so it accounts for the increased heat associated with ovulation.

development of dominant follicle which will cause sudden rise in estrogen> positive estrogen feedback switch > LH surge > ovulation > CL formation > increased P4 > increase BBT. all are very dependent on the previous.


What happens with the RAS system during pregnancy?


Estradiol from the placenta activates the RAS. However all that is promoted is the aldosterone secretion for the increase of intravascular volume necessary during preganancy.

Progesterone and relaxin from the corpus luteum prevents the vasoconstriction that would be activated via the RAS system.


Describe the milk let down pathway


During gestation, mother is making PRL. PRL is leading to milk production but it stays sequestered because estrogen + progesterone is inhibiting milk secretion.

In the meantime, estrogen > develops breast ductal epithelium and progesterone > breast alveoli. Preparing for milk secretion.

Post-partum: when the baby suckles, there is a oxytocin release that leads to low estrogen and low progesterone, milk letdown is uninhibited.


What affects the rate limiting step of 20,22 desmolase?

  1. Acute exposure to ACTH stimulation activates the rate limiting step. Chronic also upregulates cortisol forming enzymes and LDL receptors.
  2. AII also speeds up the rate limiting step, thereby responsible for the secretion of aldosterone.

Describe addison’s disease and why it leads to hyperpigmentation.


Specifically Addison’s disease is a primary hypoadrenalism disease.

That means not as much cortisol is being produced and at the same time, a lack of negative feedback.

This is required to have hyperpigemntation. iF it was at the level of the hypothalamus or pituitary, they would not have hyperpigmentation.

The reason is with a lack of cortisol, ACTH production will be ramped up and ACTH is also responsible for the processing of melanocyte stimulating hormone sequence.


What does thyroid hormone do to vascular smooth muscle?


It is vasodilatory. Why would it be vasodilatory?

Because you want to increase body temperature and release the heat that is being produced by metabolism.

So hypothyroid - they are always cold because their blood vessels vasoconstrict.

Diastolic hypertension.


Hashimoto symptoms


cold intolerance