Flashcards in adrenal physiology Deck (37):
Function of adrenal cortex
secretes steroid hormones: mineralcorticoids (aldosterone), glucocorticoids (cortisol), and sex steroids
Which part of the adrenal cortex secretes mineralcorticoids
zona glomerulosa (outer)
Which part of the adrenal cortex secretes glucocorticoids
zona fasciculata (middle)
Which part of the adrenal cortex secretes sex hormones
zona reticularis (inner)
What is the fetal zone
a region in the inner zone which is only present during fetal life and serves as an important source of precursor for estrogen synthesis by the placenta
1. Identify the key steps in steroid hormone biosynthesis.
circulating LDL > release of Cholesterol by removal of esters (inside cell) > pregnenolone (20,22 desmolase in mitochondria)
compare enzymes in different regions of the adrenal cortex
All zones contain desmolase. Zona glomerulosa lacks 17a-hydroxylase and so cannot make glucocorticoids or sex steroids. Inner zone has high activity of 11B-hydroxylase required for cortisol synthesis
Congenital defect in 21-hydroxylase, which is required for the conversion of 17-hydroxyprogesterone and progesterone to the precursors of cortisol and aldosterone, 11-deoxycortisol and 11-deoxycorticosterone, respectively. Cortisol and aldosterone are not produced, adrenal androgens increases
has ketones at carbons 3 and 20 and hydroxyls on carbons 11, 17 and 21
2. Describe the transport of glucocorticoids in the plasma.
Cortisol circulates primarily (90%) bound to proteins. Only 10% circulates in a free form. Of the 90% that is bound, 75% is bound to cortisol binding globulin (CBG) and 15% is bound to albumin.
Benefits of cortisol protein binding
increases the plasma concentration of hormone, prevents its excretion by the kidney, prolongs its half-life and serves as a reservoir of extra hormone. If the binding protein is elevated, the total concentration of hormone in the plasma is elevated but the biological activity of the hormone is unchanged, because it is the concentration of free hormone (set point) that is regulated
Actions of glucocorticoids
1. glucose mobilization. 2. lipolysis and deposition of adipose tissue on trunk, abd, face and mobilization from extremities. 3. Excretion of water (cortisol inhibits ADH). 4. Gastric acid secretion. 5. stimulates synthesis of phenyl-N-methyl Transferase (PNMT) thus increasing the production of epinephrine from norepinephrine. 6. Anti-inflammatory/ immunosuppressants
How do glucocorticoids mobilize glucose
1. stimulation of gluconeogenesis in the liver. 2. Increased proteolysis in muscle and other soft tissues providing amino acid substrates for gluconeogenesis.
Negative affects of high levels of cortisol
Catabolic actions: Muscle weakness, thinning of the skin and increased capillary fragility leading to easy bruisability. Also interfere with calcium absorption and/or bone formation, so that osteoporosis and bone fractures are a common side effect
List synthetic glucocorticoids
Dexamethasone (powerful), Prednisone, triamcinolone, hydrocortisone.
Which synthetic glucocorticoids can be used in Addisons disease
Hydrocortisone and prednisone also have considerable mineralocorticoid potency and can be used in cases of Addison's disease where both gluococorticoid and mineralocorticoid secretions are compromised
4. Diagram the regulation of ACTH production and release.
CRH (hypothalamus) > ACH (ant. Pituitary) > cortisol (zona fasciculata) > cortisol negatively feedsback on hypothalamus and pituitary to inhibit CRH and ACTH secretion
How does ACTH increase cortisol secretion
In the cortex, ACTH leads to elevated cAMP levels, which in turn increase the rate of synthesis of pregnenolone. LDL uptake is also enhanced, as is hydrolysis of stored cholesterol esters and transport of cholesterol into mitochondria
Cortisol fluctuation thorughout the day
Elevated at time of waking in morning and decreased at the onset of sleep
How does stress affect cortisol
Stress can override cortisols negative feedback on CRH and ACTH resulting in up to a 40-fold increase in cortisol secretion. Individuals who are not able to respond to stress with increased cortisol secretion have increased morbidity.
Adrenal androgen regulation
Adrenal androgens are stimulated by ACTH
Regulation of mineralcorticoid secretion
Aldosterone is regulated by the renin-angiotensin system. It is only minimally influenced by ACTH. Decreased plasma volume or sodium OR BP > Renin release (juxtaglomerular apparatus of kidney) > renin converts angiotensinogen to angiotensin 1 > degraded to angiotensin II > stimulates aldosterone secretion
Actions of aldosterone
stimulate sodium absorption, potassium, and hydrogen ion excretion in the renal tubule. Also spares sodium in sweat glands in hot, humid environments
Metabolism of steroid hormones
they undergo reactions in the liver that tend to both reduce their activity and increase their water solubility. The metabolites are then excreted in the urine providing a convenient medium for assessing their secretion
Primary adrenal insufficiency
Aka Addisons disease: an infectious process (e.g., tuberculosis, fungal disorders, autoimmune response) wipes out the entire adrenal cortex. It is life threatening and both mineralocorticod and glucocorticoid secretion is deficient. Symptoms include weakness, weight loss, hyponatremia, hyperkalemia, GI problems. ACTH is not subjected to negative feedback and it is elevated leading to hyperpigmentation. Glucocorticoid and mineralocorticoid activities must be replaced.
Secondary adrenal insufficiency
Due to ACTH insufficiency. Only glucocorticoids need to be replaced. It usually occurs as a general defect in the anterior pituitary (panhypopituitarism).
Increased plasma aldosterone can result from a tumor of the adrenal cortex (primary) or inappropriately high activity of the renin-angiotensin system (secondary). Symptoms include hypertension in the case of primary hyperaldosteronism, hypokalemia, and alkalosis.
Congenital adrenal hyperplasia
Congential defects in the 21-hydroxylase or 11b-hydroxylase pathways of steroidogenesis decrease the synthesis of adrenal corticoids so that the negative feedback pathway controlling ACTH release is defective. The resultant increased ACTH stimulates steroidogenesis and precursors accumulate as well as hormones whose synthesis is not affected (e.g. adrenal androgens in some cases). In females, a common symptom is masculinization.
Excessive secretion or levels of cortisol. Central obesity, moon facies, dorsocervical fat deposits, and supraclavicular deposits. Hirsutism, thinning of skin with purple striae, easy bruising, slow wound healing. Muscle weakness, osteoporosis, insomnia, depression
What is the adrenal medulla derived from
neural crest- it is a specialized sympathetic ganglion.
Adrenal medulla structure
Contain cells called adrenal chromaffin cells which are stimulated by nerve endings of cholinergic preganglionic fibers of SNS
Function of adrenal medulla
Ach from cholinergic preganglionic cells act on cholingergic receptors on chromaffin cells to release the catecholamine hormone epinephrine, and to a lesser extent, norepinephrine (NE). Ca dependent exocytosis
Synthesis of epi and NE
Rate limiting enzyme in chromaffin cells is tyrosine hydroxylase, a cytosolic enzyme that converts tyrosine to dihydroxyphenylalanine > converted to dopamine > taken up in secretory granules and coverted to NE then epi
compare alpha and beta adrenergic receptors G proteins
Beta: Gs, stimulates adenylate cyclase and cAMP. Alpha1: Gq, PLC pathway. Alpha2: Gi/o, inhibits cAMP production
compare epi and NE activation of adrenergic receptors
epi: Beta > alpha. NE: alpha > Beta (no Beta 2)
What stimulates release of epinephrine
Perception or even anticipation of danger, trauma, pain, and other physiological stressors like hypovolemia, hypotension, hypoglycemia, and exercise. Final common pathway is activation of cholinergic fibers in greater splanchnic nerve. Activaion of nicotinic acetylcholine receptors (nAChRs) (and possibly muscarinic acetylcholine receptors (mAChRs)) leads to release of catecholamines