Adrenal Learning Material

Adrenal • Adrenal Glands • The outer part is called the adrenal cortex, which produces many different hormones called corticosteroids including cortisol. • • • • • • These hormones regulate the : salt and water balance in the body, prepare the body for stress, regulate metabolism, interact with the immune system, and induce sexual function. • The inner part, which is called the adrenal medulla, produces catecholamines, such as epinephrine. • Epinephrine also known as adrenaline, increases the blood pressure and heart rate during times of stress. • adrenal cortex is consisted of 3 zonas, including : • glumeruloza, • Fasiculata • and reticulata • Hormones of adrenal cortex: Three general classes of steroid hormones based on predominant functions Mineralocorticoids: 21 carbon containing steroids , synthesized by zona glomerulosa, regulate water and electrolyte balance. Aldosterone is the most prominent mineralocorticoid. Glucocorticoids: Also 21 carbon steroids, produced mostly in zona fasciculata and affect glucose (hence the name), amino acid and fat metabolism. Cortisol (also known as hydrocortisone) is the most important GC in humans. Androgens: The zona reticularis and fasciculata produce significant amounts of androgen precursor DHEA (dehydroepiandrosterone) and androstenedione (both 19 carbon). • Synthesis of Adrenocortical Hormones • Made from cholesterol taken from LDL-c in the blood and stored in adrenocortical cells • Adrenocortical cells stimulated by ACTH or cAMP. • Cholestrol • Synthesis of Adrenocortical Hormones • Cortisole is the main glucocorticoid hormone that is produce in fasciculate section of adrenal cortex with 21 carbon • Plasma Transportation • Cortisol circulates in plasma bound to proteins or as free. • Transcortin or corticosteroid binding globulin (CBG) binds cortisol. • Most of the steroid hormones bind to CBG. • Cortisol binds to CBG and has a half life of 1.5 - 2 hrs. • 8-10% Cortisol is free. • Progesterone and deoxycorticosterone also bind to CBG strongly. • Corticosterone binds to CBG with less affinity. • Aldosterone does not have a specific protein but binds weekly with albumin 72 • Androgens: • Are excreted as 17-keto compounds including DHEA (sulfate) as well as androstenedione and its metabolites. • Small amounts of testosterone secreted by adrenals are also converted to 17-keto compounds like androsterone and etiocholanolone which are excreted in urine • Metabolic functions of adrenal corticosteroids • Glucocorticoid hormones: the most important are Cortisol, cortisone and Corticosterone • Effects on Carbohydrate metabolism: • ↑es Gluconeogenesis and glucose output • ↑es amino acid utilization • ↑es glycogen storage • ↓es glucose uptake by tissues other than liver • Effects on Lipid metabolism: • ↑es lipolysis • ↑es circulating free fatty acids (FFA) • ↓ es utilization of FFA for TG synthesis • Metabolic functions of adrenocorticosteroids • Effects on Protein metabolism: • ↑es degradation of proteins in extra hepatic tissues • ↑es protein synthesis in liver • Effects on Nucleic acid metabolism: • promotes transcription of specific genes in liver. • Effects on water and electrolyte metabolism: • Mediated through ADH ,Deficiency causes ↑ ADH which decreases glomerular filtration and leads to water retention. • Hormones of the Adrenal Cortex • Metabolic functions of adrenocorticosteroids Androgens: DHEA and androstenedione are precursors of testosterone which is the most potent androgen. General Biochemical functions of androgens are: • Growth, development and maintenance of male reproductive organs • Effect of androgens on protein metabolism: promote protein synthesis , positive nitrogen balance and increase muscle mass. • Effect on carbohydrate and fat metabolism: increase glycolysis, lipolysis and TCA cycle • Effect on mineral metabolism: Promote the mineral deposition and bone growth. • Mineralocorticoid hormones: the most active and potent mineralocorticoid is Aldosterone. • ↑es reabsorption of sodium by the distal convoluted tubules of kidney. • Water follows sodium , thus leads to water retention • ↑es Excretion of K+, H+ and NH+4 ions in urine. • Acts on all epithelial cells that exchange Na+ and water( kidney , GI tract , salivary glands etc) • Promotes synthesis of transporter of proteins (pumps) which facilitate Na+ and water movement across cell membranes. • Regulation of glucocorticoids • The Secretion of glucocorticoids from the adrenal cortex is regulated by negative feedback involving the CRH secretion by the hypothalamus. • CRH then acts on the anterior pituitary to stimulates ACTH secretion, which then stimulates the adrenal cortex into cortisol secretion • Hormones of the Adrenal Cortex CUSHING’S DISEASE (TOO MUCH CORTISOL) • secretion of cortisol from adrenal cortex • 4X more frequent in females • Usually occurs at 35-50 years of age ETIOLOGY Cushing’s • • • • Primary-tumor on the adrenal cortex Secondary-tumor on the anterior pituitary gland Ectopic ACTH secreting tumor (lung, pancreas) Iatrogenic-Steroid administration • immune response – More prone to infection – resistance to stress – Death usually occurs from infection • Adrenal Medulla Cortex 1 • In response to stimulation, chromaffin cells secrete the hormones epinephrine (adrenaline) and norepinephrine (noradrenalin) directly into the blood 2 3 Medulla • Catecholamines stored in large vesicles chromaffin cells of the adrenal medulla within • Chromaffin cells innervated by neurons of the sympathetic nervous system ‘Fight or flight’ response • The medulla is involved in extreme stress and, within this context, epinephrine and norepinephrine both work with cortisol from the adrenal cortex. • Epinephrine and norepinephrine important mainly in crisis situations are • Cathcolamines Synthesis Tyrosine is precursor for the synthesis of catecholamines. 2. The catecholamine are produced in response to fight, fright and flight (3F). These include emergencies like shock, cold, fatigue, emotional condition like anger • Biochemical function of catecholamine . 1- Effect on carbohydrate metabolism: Both of them can increase glycogenolysis and gluconeogenesis and decrease glycogenesis. . • 2-Effect on lipid metabolism: • Both of them enhance the breakdown of TAG in adipose tissue. • This cause increase in the free fatty acid in the circulation which are effectively utilized by the heart and muscle as fuel source. • 3. Effect on physiological function: • Cateccholamines increase cardiac output, blood pressure and oxygen consumption. • They cause smooth muscle relaxation in bronchi, GIT and blood vessels supplying skeletal muscle • phaeochromocytoma (PCC) or pheochromocytoma: • A neuroendocrine tumor of the medulla of the adrenal glands (originating in the chromaffin cells), • or extra-adrenal chromaffin tissue secretes excessive amounts of catecholamines(usually adrenaline (epinephrine) ] if in the adrenal gland and not extra-adrenal, and noradrenaline (norepinephrine). • Here's a look at pheochromocytomas the extra-adrenal sites • 1. Within the sympathetic nerve chain along the spinal cord (orange spots) • 2. Overlying the distal aorta (the main artery from the heart) (green spots) • 3. Within the ureter (collecting system from the kidney (yellow spot) • 4. Within the urinary bladder (blue spot) • 5. Remember, 90% are in the adrenal glands (red spots on the kidneys) of