Endocrine Physiology The Adrenal Gland 1 Dr.Mouaadh abdelkarim Assistant Professor of Physiology Department of Physiology 2 nd floor Tel:

 Describe the cellular arrangements and functional components of the adrenal gland.  List the hormones secreted by the medulla and cortex of the adrenal gland.  Summarize regulation of secretion of adrenocortical steroids.  Discuss regulation of aldosterone secretion.  List the major stimuli for aldosterone secretion.  Explain how negative feedback regulates aldosterone secretion.  Explain regulation of glucocorticoid and adrenal androgen secretion.  List the trigger(s) for cortisol secretion.  Describe the physiological actions of aldosterone.  Outline the actions of glucocorticoids.  Summarize the actions of adrenal androgens.  Describe the causes and major manifestations of hyperadrenocorticism and Hypoadrenocorticism  Describe circumstances in which catecholamines are released from the adrenal gland.  List the major actions of catecholamines. Learning outcomes After reviewing the PowerPoint presentation, lecture notes and associated material, the student should be able to:

Cortex Medulla Adrenal glands are paired, pyramid-shaped organs at the top of the kidneys. Weigh 6-10 g. Structurally and functionally, they are two glands in one Adrenal cortex (80-90%)– glandular tissue derived from embryonic mesoderm Adrenal medulla (10-20%)– formed from neural ectoderm, can be considered a modified sympathetic ganglion Adrenal (Suprarenal) Glands

Synthesizes and releases steroid hormones (corticosteroids) Different corticosteroids are produced in each of the three layers: Zona glomerulosa – mineralocorticoids (mainly aldosterone) Zona fasciculata – glucocorticoids +Androgens (mainly cortisol and corticosterone) Zona reticularis – gonadocorticoids + glucocorticoids (mainly dehydroepiandrosterone DHEA) Adrenal Cortex

Adrenal Gland Guyton and Hall

Adrenal Cortex Guyton and Hall Salt Sugar Sex

HPA Axis Guyton and Hall

Steroid Hormones: Structure Guyton and Hall

Steroid Hormones Synthesis Steroids are derivatives of cholesterol Cholesterol is from the lipid droplets in cortical cells Removed cholesterol is replenished by cholesterol in LDL in blood or synthesized from acetate - LDL is a complex composed of cholesterol, phospholipids, triglycerides, and proteins (proteins and phospholipids make LDL soluble in blood). - LDL is taken into cells via LDL receptors, and broken down into esterified cholesterol, and then free cholesterol:

Steroid hormones are synthesized and secreted on demand (not stored) The first and rate-limiting step in the synthesis of all steroid hormones is conversion of cholesterol to pregnenolone by the enzyme cholesterol dismolase (cholesterol side chain cleavage enzyme (SCC)) Newly synthesized steroid hormones are rapidly secreted from the cell Following secretion, all steroids bind to some extent to plasma proteins: CBG (corticosteroid binding globulin) and albumin Steroid Hormones Synthesis (Cont.)

Steroidogenesis: Steroidogenesis entails processes by which cholesterol is converted to biologically active steroid hormones

Genetic Defects in Adrenal Steroidogenesis Congenital adrenal hyperplasias : Congenital adrenal hyperplasia (CAH) are any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands (steroidogenesis). ACTHِAdrenal hyperplasiacortisol

21-hydroxylase (P450c21) deficiency: cortisol, corticosterone, and aldosterone deficiency *ACTH Adrenal hypertrophy and high amounts of androgen * Virilization of female (masculanization) Congenital adrenal hyperplasias

Steroid Hormones: Action Guyton and Hall

production mg/day concentr. ng/ml activity MINERAL. activity GLUCO. aldosterone % deoxycorti- costerone /15 corticoste- rone /504% cortisol /40095% DHEA7-155 Hormones of adrenal cortex

1- Cortisol is at 1000 fold higher concentrations than aldosterone 2- Corticosterone >>>>aldosterone 3- Cortisol binds well to the mineralocorticoid receptor

Mineralocorticoids: Aldosterone A steroid hormone. Essential for life. Synthesized in zona glomerulosa Responsible for regulating Na + reabsorption in the distal tubule and the cortical collecting duct Target cells are called “principal (P) cell”. It also affects Na+ reabsorption by sweat, salivary and intestinal cells. * Stimulates synthesis of more Na/K-ATPase pumps.

Aldosterone secretion is stimulated by: Decreasing blood volume or pressure (renin- angiotensin system). Rising blood levels of K + Low blood Na + ACTH Mineralocorticoids: Aldosterone

Voltage-sensitive calcium channels open and the intracellular calcium concentration increases—activating calcium calmodulin kinase. Calcium channel blockers inhibit aldosterone synthesis. Aldosterone synthesis

Aldosterone levels fluctuate diurnally— highest concentration being at 8 AM, lowest at 11 PM, in parallel to cortisol rhythms.

Renin-angiotensin mechanism – kidneys release renin, which stimulates angiotensin II that in turn stimulates aldosterone release Plasma concentration of potassium and sodium– directly influences the zona glomerulosa cells ACTH – causes small increases of aldosterone during stress Atrial natriuretic peptide (ANP) – inhibits activity of the zona glomerulosa The Four Mechanisms of Aldosterone Secretion

Guyton and Hall

Actions of Aldosterone Stimulates sodium reabsorption by distal tubule and collecting duct of the nephron and promotes potassium and hydrogen ion excretion Increases transcription of Na/K pump Increases the expression of apical Na channels and an Na/K/Cl cotransporter Expands ECF volume

Aldosterone binds to the mineralocorticoid receptor in target cells and affects transcriptional changes typical of steroid hormone action. The kidney is the major site of mineralocorticoid activity.

Aldosterone: Role in diseases Complete failure to secrete aldosterone leads to death (dehydration, low blood volume). Hyperaldosterone states: Contribute to hypertension associated with increased blood volume.

Overproduction of aldosterone primary causes, ie. Conn’s syndrome adenoma, nodular hyperplasia of zona glomerulosa secondary cirrhosis, ascites, nephrotic syndrome symptoms, signs headache, hypokalemia causing muscle weakness, hypernatremia, hypervolemia, nocturnal polyuria, hand cramping

Overproduction of aldosterone treatment surgical for adenoma Spironolactone

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