Flashcards in Adrenal Gland Physiology Deck (21):
Adrenal cortex functions
secretes steroid hormones: mineralocorticoids, glucocorticoids and sex steroids
Zones of adrenal cortex
Zona glomerulosa: produces aldosterone (salt balance)
Zona Fasciculata: cortisol (most important glucocorticoid)
Zona reticularis (innermost): adrenal androgens
"Ga, Fc, Ra"
1. Cholesterol is precursor for adrenal hormones, mostly from circ LDL
2. Once in cell, cholesterol is removed, esterified, stored in lipid droplets. (Cortex can also synthesize cholesterol from acetyl Co-A)
3. Cholesterol released from lipid droplets by removing esters.
4. **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 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)
-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
-Vary with the secretion of cortisol
-stimulated by ACTH (and increased at puberty)
-especially imp for female libido and growth of pubertal hair
-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.
-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
-only glucocorticoids need to be replaced
-General defect in the anterior pituitary (panhypopituitarism)
-central obesity, moon facies, buffalo hump (dorsocervical region)
-Thinning of skin
-purple striae, easy bruising, slow wound healing
-Cortisol has CNS effects so: emotional lability, insomnia, poor memory, euphoria, mild depression; in extreme cases, psychosis and severe depression
-derived from neural crest
-cells: adrenal chromaffin cells, stimulated by nerve endings of cholinergic preganglionic fibers of symp nervous system (ACh release to promote release of epi, norepi)
-Epi, norepi: Ca dependent exocytosis from chromaffin cell
Rate limiting step of epi/norepi synthesis in chromaffin cells
-converts tyrosine to dihydroxyphenylalanine
-compound is converted to dopamine in cytosol
-DA taken up in the secretory granules where it is converted to norepi, then epi
Actions of catecholamines
-Beta adrenergic receptors stimulate adenylate cyclase and thus cAMP is the 2nd messenger
-alpha 2 adrenergic receptor is coupled to Gi and inhibits cAMP production
-alpha 1 activate the PLC signaling pathway
-Epi activates Beta adrenergic receptors better
-Norepi activates alpha adrenergic receptors better
Regulation of catecholamine release
-stressors (danger, trauma, pain; hypovolemia, hypotension, hypoglycemia) trigger epi secretion
-responses initiated at hypothalamus and brainstem
-Final pahtway: activation of cholinergic greater splanchnic nerve. ACh released from nerve onto chromaffin cells
-nAChRs are major mediator of cholingergic control (mAChRs to lesser extent)
-nAChRs lead to cation flux into the chromaffin cell, depolarization, activation of calcium influx. Also Ca flux through nAChRs.
-Release of catecholamines via Ca-dependent exocytosis