Adrenal Cortex Phys- Trachte Flashcards
What are the three zones of the adrenal cortex?
Zona Glomerulosa
Zona Fasiculata
Zone Reticularis
Which zone of the adrenal cortex secretes aldosterone?
Zona glomerulosa
Aldosterone = mineralcorticoid
Which zone makes cortisol (glucocorticoid)
Zone fasiculata
Which zone makes sex hormones (androgens)?
Zone Reticularis
Describe the glucocortiocoid endocrine axis
Hypothalamus secretes CRH
Anterior pituitary secretes ACTH
Adrenal cortex secretes cortisol
Cortisol acts on immune system, liver, muscle, and adipose tissue
What kind of receptor does CRH bind on corticotrophs in anterior pituitary?
Gs-protein coupled receptor Stimulates adenylate cyclase Increases cAMP Increased synthesis of POMC POMC is cleaved to produce: MSH ACTH Liptropin
What 3 things are proudced during cleavage of POMC in corticotrophs of the anterior pituitary?
ACTH
MSH
Lipotropin
What does MSH do?
Stimulates melanocyte proliferation and pigmentation
What receptor does ACTH bind?
Melanocortin-2-receptor in adrenal cortical cells
Gs coupled receptor
Elevates cAMP
Starts signal transduction cascade involving PKA
What cancer usually causes ectopic production of ACTH?
Small Cell lung cancer
What is the rate-limiting step in adrenal steroid synthesis?
Production of “side chain cleavage enzyme” in the adrenal cortex
*This enzyme is required for cholesterol conversion to pregnenolone
What enzyme is required for cholesterol conversion to pregnenolone?
Side-chain cleavage enzyme (CYP11A = P450scc)
Where would you find glucocorticoid receptors? What is the sequence of events?
Cytosol! Belong to the nuclear receptor super family
Hormone bound receptor moves to nucleus and forms homodimers
Homodimers act as transcription factors - bind to Glucocorticoid Response elements
Initiate OR inhibit transcription
Regulates development, metabolism, and immune repsonse
The mineral corticoid receptor has equal affinity for aldosterone and cortisol…. cortisol is much more abundant than aldosterone…… how does aldosterone responsive tissue prevent cortisol from binding to the MR?
In aldosterone-responsive cells cortisol is enzymatically converted to cortisone = a metabolically inactive steroid so has no affect (and can’t bind receptor)
What is the primary active glucocorticoid?
Cortisol!
What is 90% of cortisol bound to in circulation?
60% = CBG = corticotropin binding globulin = transcortin
30% = albumin
What happens to bone at sustained elevation of glucorticoids?
Decreased osteoblast activity - decreased bone mass - osteoporosis
What is Cushing Syndrome?
Excessive secretion of cortisol
May be due to a variety of causes
If Cushing syndrome is due to excess ACTH secretion (thus increased cortisol) what is normally the cause?
Pituitary Adenoma
Why do you see hyperpigmentation in pituitary adenomas?
Increased POMC!! Remember it produces ACTH, Lipotropin, and MELANOCYTE-STIMULATING HORMONE!
Those melanocytes are working like craaaaaazy!
If Cushing syndrome is due to primary glandular excess production of cortisol (like an adrenal tumor) what would the blood profile look like?
Increased cortisol
BUT DECREASED ACTH (from negative feedback)
What would the blood profile look like in a pituitary adenoma?
Increased ACTH (due to the adenoma) Increased Cortisol Low CRH (negative feedback)
Effect on CRH, ACTH, and cortisol:
Hypothalamic damage resulting in no CRH secretion
- Low CRH
- Low ACTH
- Low Cortisol
Effect on CRH, ACTH, and cortisol:
Pituitary damage resulting in no ACTH secretion
- Low ACTH
- Low Cortisol
- High CRH
Effect on CRH, ACTH, and cortisol:
Adrenal damage resulting in no cortisol secretion (Addison’s disease)
- Low cortisol
- High CRH
- High ACTH
Effect on CRH, ACTH, and cortisol:
Receptor damage resulting in no efficacy of cortisol
- High cortisol
- High ACTH
- High CRH
Effect on CRH, ACTH, and cortisol:
Tumor secreting excess CRH
- High CRH
- High ACTH
- High Cortisol
Effect on CRH, ACTH, and cortisol:
Tumor secreting excess ACTH (Cushing’s)
- High ACTH
- High Cortisol
- Low CRH
Effect on CRH, ACTH, and cortisol:
Tumor secreting excess cortisol
- High Cortisol
- Low ACTH
- Low CRH
What 3 enzymes can causes congenital adrenal hyperplasia?
17 a-hydroxylase
21-hydroxylase
11B-hydroxylase
What causes congenital adrenal hyperplasia?
Adrenal enzyme deficiency characterized by enlargement of both adrenal glands due to increased ACTH stimulation (due to decreased cortisol production)
What are all steroids made from?
Cholesterol!
What is Addison’s disease?
Immune mediated destruction of adrenal cortex
decreased production of cortisol and aldosterone
Compensatory increase in POMC (increased ACTH and MSH)
Thus you get hyperpigmentation!
Does aldosterone exhibited negative feedback on ACTH secretion?
NO!!!!!!
