Adrenal Cortex

Question 1

functional zonation of adrenal glands

Answer 1

Zona fasculata reticularis makes cort and androgens

zona glomerulosa makes aldosterone

Question 2

Cell mechanism of activation of steroidogenisis in zona fasculata/reticularis

Answer 2

1. ACTH binds to its G-coupled protein receptor
2. low density lipoprotein (LDL) is taken up and cholesterol esters are stored in lipid droplets
3. ACTH increases cAMP production to increase (cholesreol ester hydrolase) and increases STAR activity
4. cholesterol is trasported from lipid droplet to mito via STAR (rate limiting step)
5. steroidogenisis, cort is diffused right out of the cell via simple diffusion

STEROIDOGENISIS: look at RAFF ADRENAL SLIDES

Question 3

synthetic cort

Answer 3

prednisones bind more tightly to CBGs

Question 4

Mechanism of glucocorticoid receptor

Answer 4

1. Cort dissociates from the CBG and diffuses right into the cytoplasm
2. Cort binds to GR (glucocorticoid receptor) and causes it to dissociate from its HSP complex
3. the 2x (cort/GR) enters the nucleus and attaches to 2x GRE (glucocorticoid response elements) right on the DNA–> transcription and translation–> change in cell response

Question 5

POMC gene

Answer 5

ACTH etc are produced by post transcriptional modification of the POMC gene, by processing prohormone convertase 1 and 2 (PC1 and PC2)

Specific tissues express PC1 (ant pit) and PC2

Question 6

primary adrenal insufficiency vs secondary

Answer 6

primary aka adissons disease: Adrenals are fucked up–> very low cort levels, which cause super high ACTH because of a lack of negative feedback
(weakness, fatigue, anorexia, wt loss)

secondary: messed up ant pit not making ACTH, so Adrenals atrophy, low cort levels

Question 7

Causes of Primary adrenal insufficiency

Answer 7

Autoimmune (80%) TB(20%)

Question 8

Top 4 symptoms of Adrenal insufficiency

Answer 8

Weakness, fatigue, anorexia, weight loss
Hyperpigmentation occurs in primary only (MSH receptor)
Hypotension is due to the loss of CORT maintenance of vasoconstriction (permissive because CORT is needed to help the vaso constrictors do their job)

Question 9

Recovery from Gluccocorticoid therapy

Answer 9

patients need to be weaned off of gluccocorticoid therapy , because once GC is taken off, Plasma ACTH starts to increase due to loss of negative feedback, however it takes months for the hypothalamus and pituitary to wake up and for the Adrenals to regrow

Question 10

Cushings Syndrome Subtypes

Answer 10

ACTH dependent (pituitary of ectopic tumor making tooo much ACTH, over stimulation of the Adrenals)

ACTH independent (adrenal tumor making cort in the absence of ACTH)