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Adrenocortical Hormones
Adrenocortical Hormones
by Dr.Maulik Varu
Adrenal cortex
Three parts (1) zona glomerulosa (2) zona fasciculata (3) zona reticularis
Adrenal Histology
Zona glomerulosa
A thin layer of cells that lies just underneath the capsule. 15% of adrenal cortex. Secretes mineralocorticoids especially significant amount of aldosterone by enzyme aldosterone synthase. controlled by angiotensin-II and potassium.
Zona fasciculata
Middle and widest layer. 75% of adrenal cortex. Secretes glucocorticoids as well as small amounts of androgens and estrogens. Controlled by hypothalamic-pituitary axis via ACTH.
Zona reticularis
Deep layer Secretes androgens mainly
dehydroepiandrosterone Androstenedione
Controlled by ACTH and cortical androgen stimulating hormone released from pituitary gland.
source
All human steroid hormones including those produced by adrenal cortex are synthesized from cholesterol. 80% of cholesterol provided by LDL. 20% by de novo synthesis.
Pathway of synthesis
Metabolic fates
Approx. 90-95% of cortisol in the plasma binds to plasma proteins especially a globulin called cortisol binding globulin or transcortin and to a lesser extent to albumin. Only about 60% of aldosterone binds to plasma proteins, 40% is in the free form.
Degraded mainly in the liver and conjugated to form glucuronic acid and to a lesser extent , sulfates. 25%- excreted in bile Remaining enter the circulation ,filtered by the kidneys and excreted in urine.
Mineralocorticoids
Aldosterone Desoxycorticosterone Corticosterone 9-fluorocortisol Cortisol Cortisone
Glucocorticoids
Cortisol Corticosterone Cortisone prednisolone Methylprednisolone Dexamethasone
Normal values
Aldosterone:-6 nanograms/100ml -secretory rate-150 micrograms/day Cortisol:-12 micrograms/100ml -secretory rate-15 to 20mg/day
Functions of mineralocorticoidsaldosterone
Renal and circulatory effects:increases renal tubular reabsorption of sodium and secretion of potassium especially in the collecting tubules and to a lesser extent in the distal tubules and collecting ducts.
Effect on potassium ions. Effect on hydrogen ions. Effect on sweat glands,salivary glands and intestinal epithelial cells.
Mechanism of action
Because of its lipid solubility aldosterone diffuses readily to the interior of the tubular epithelial cells. Combines with cytoplasmic receptor protein and form aldosterone-receptor complex. Diffuses into the nucleus and form m-RNA m-RNA diffuses back into the cytoplasm and in conjuction with the ribosomes causes protein formation.
Regulation
(1) potassium ion concentration (2)renin-angiotensin system (3) sodium ion concentration (4) ACTH
Functions of glucocorticoids
On carbohydrate metabolism
Stimulation of gluconeogenesis Decreased glucose utilization by the cells Effect on insulin adrenal diabetes.
On protein metabolism
Reduction in cellular proteins. Increased blood amino acids,diminished transport to extrahepatic cells and enhanced transport to hepatic cells Increase in liver and plasma proteins.
On fat metabolism
Mobilization of fatty acids from adipose tissue Obesity by excess cortisol
Resistance of stress.
-trauma -infection -intense heat or cold -surgery -any debilitating disease
Mobilization of amino acids and fats from cellular stores for energy and synthesis of other compounds including glucose
Amino acids provide purines, pyrimidines and creatine phosphate which are necessary for maintainance of cellular life and reproduction of new cells
Anti-inflammatory effects
Stabilizes the lysosomal membrane. Decreases capillary permeability. Decreases migration of WBC towards inflammed area. Lowers fever mainly by reducing release of interleukin-I from WBC. Inhibits phagocytosis. Resolution of inflammation.
Other effects
On allergic reactions On blood cells
Mechanism of action
Due to lipid solubility diffuse through the cell membrane Hormone-receptor complex in cytoplasm Interacts with specific regulatory DNA sequences called glucocorticoids response elements Change in gene transcription to alter synthesis of m-RNA for the proteins that mediate their multiple physiological effects
Regulation of secretion
ACTH It activates adenylyl cyclase in the cell membrane which induces the formation of cAMP in the cytoplasm The cAMP in turn activates intracellular enzymes that cause formation of adrenocortical hormones
ACTH
Control by CRF Influence of physical or mental stress Negative feedback
Circadian rhythm
Adrenal androgens
Most important is dehydroepiandrosterone especially during fetal life Weak effects in humans Growth of pubic and axillary hairs in females Some androgens are converted to testosterone
Hypoadrenalism-Addisons disease
Causes
Clinical features
Hyponatremia ,hyperkalemia,acidosis Hypotension Weakness Pigmentation of skin and mucus membrane Shock If untreated-death within 4 days to 2 weeks
Addisonian crisis
In a person with addisons disease the critical need for extra glucocorticoids and associated severe debility in times of stress is called addisonian crisis.
cushings syndrome
Exogenous glucocorticoids ACTH producing pituitary tumours Cortisol secreting adrenal adenoma or carcinoma Ectopic ACTH production by non pituitary tumours Ectopic CRH production by non hypothalamic tumours
Clinical features
Moon face Buffalo torso Purple striae Thin limbs Osteoporosis Impaired wound healing diabetes hypertension Acne,hirsutism
Conns syndrome
Primary aldosteronism Due to small tumour of zona glomerulosa cells Increase in ECF and blood volume Hypokalemia hypertension
21-hydroxylase deficiency(complete) -most common variety. -hypotension,hyperkalemia. -virilization in females. -precocious puberty in males. -In adult males diagnosis is not so obvious since the external genitalia are normal unless there is family history. 21-hydroxylase deficiency(partial) -normal BP.
17-hydroxylase deficiency -hypertension -primary amenorrhoea and failure of development of secondary sexual characters. 11-hydroxylase deficiency -hypertension -virilization in females -may be mistaken for cushings syndrome but there is no glucose intolerance,obesity and protein wasting. 3- hydroxysteroid dehydrogenase def -partial masculinization of external genitalia of females due to hypersecretion of DHEA -male pseudohermaphroditism.
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