Adrenal Gland Physiology Flashcards
Adrenal cortex functions
secretes steroid hormones: mineralocorticoids, glucocorticoids and sex steroids
DHEA-S
dehydroepiandrosterone-sulfate
- sex steroid
- weak androgen
Zones of adrenal cortex
Zona glomerulosa: produces aldosterone (salt balance)
Zona Fasciculata: cortisol (most important glucocorticoid)
Zona reticularis (innermost): adrenal androgens
“Ga, Fc, Ra”
Steroidogenesis
- Cholesterol is precursor for adrenal hormones, mostly from circ LDL
- Once in cell, cholesterol is removed, esterified, stored in lipid droplets. (Cortex can also synthesize cholesterol from acetyl Co-A)
- Cholesterol released from lipid droplets by removing esters.
- **Rate limiting step requires mitochondrial enzymes: CYP450 or 20,22 desmolase: product is Pregnenolone.
Why can’t zona glomerulosa make glucocorticoids or sex steroids?
lacks 17 alpha hydroxylase
Defect in 21-hydroxylase
- enz required for conversion of 17-hydroxyprogesterone and progesterone to the precurors of cortisol (11 deoxycortisol) and aldosterone (11-deoxycorticosterone)
- So: cortisol, nor ALDO are synthesized, adrenal androgens increased.
Cortisol circulation
- cortisol is the most imp glucocorticoid
- 10% circulates free (active form, regulated), 90% circulates bound to proteins (reservoir)
- Of bound: 75% to cortisol binding globulin (CBG), 15% to albumin
Actions of glucocorticoids
- Imp actions involve glucose mobiliziation: gluconeogenesis in liver and proteolysis in muscle for aa. Cortisol is signif for maintaining or elevating blood glucose in times of stress, also strongly catabolic (can lead to muscle weakness at high levels) Cortisol can also thin the skin, lead to easy bruising. Interfere with Ca absorption/bone formation (osteoporosis, fractures).
- high doses of glucocorticoids lead to deposition of adipose tissue on trunk, abdomen, face, and mobilization from extremities
- inhibition of ADH function (increase water excretion)
- increase gastric acid secretion
- Cortisol also has paracrine effect on adrenal medulla. Stim synthesis of PNMT (phenyl-N-methyl transferase) thus increasing production of epi and norepi
- High doses of
glucocorticoids: anti-inflammatory, immunosuppressants - Cushing’s disease (hypercortisolism)
Synthetic glucocorticoids
- strong: dexamethasone
- milder: prednisone, triamcinolone
- Hydrocortisone and prednisone can be used for Addison’s (glucocorticoid and mineralocorticoid secretions)
Regulation of cortisol secretion
Negative feedback through HPA axis.
- Hypothalamus secretes CRH, AP releases ACTH (Ca-dep release, POMC gene activation). (CRH binds to recep on corticotrphs, activating adenylate cyclase)
- ACTH acts on cells of Zona fasciculata and reticularis to promote cortisol secretion
- In crtex, ACTH leads to elevated cAMP, increasing pregnenolone synthesis
- Plasma free cortisol feeds back on the hypothalamus and the pituitary to inhibit CRH and ACTH secretion, completing negative feedback loop.
- ACTH can also limit its own secretion
- Daily rhythm (high in morning, low at night) to cortisol secretion
- Cortisol secretion increases greatly with stress.
- Stress stimulates CRH, then ACTH, then cortisol release
Adrenal androgens
- Vary with the secretion of cortisol
- stimulated by ACTH (and increased at puberty)
- especially imp for female libido and growth of pubertal hair
Aldosterone regulation
- renin-angiotensin system
- min influence by ACTH
- Renin from juxtaglomerular apparatus of the kidney in response to a decrease in plasma volume or sodium, also responds to decreased BP
- Renin converts angiotensinogen to angiotensin I, degraded to ang II, which stimulates aldosterone secretion
- Aldo released in response to high plasma K+ too.
Aldosterone actions
-stimulate sodium absorption, K and H excretion in renal tubule
Metabolism of steroid hormones
cortisol t1/2 60-70 minutes
Aldosterone t1/2 of 20 minutes
-rxns in liver, then metabolites excreted in urine
Secondary adrenal insufficiency
- ACTH insufficiency
- only glucocorticoids need to be replaced
- General defect in the anterior pituitary (panhypopituitarism)