Chapter 4-Adrenal Glands 4-1

Ch. 4-- Study Guide 1.Critically read (1) pages pp before postsecretory metabolism of adrenal cortical hormones section; (2) pp (physiology of the mineralocorticoids) before Effects on water balance subsection. 2.Comprehend Terminology (the text in bold/italic) 3.Study and understand the text and corresponding figures. 4-2

4.1. Introduction 4-3

§ Introduction 1.Adrenal hormones: –required for maintenance of life –Without them, deranged electrolyte or CHO metabolism, hypoglycemic coma, and death –Outer cortex– three steroid hormones: mineralocorticoids, glucocorticoids, and androgens –Inner medullaa component of the sympathetic nervous system 4-4

4.2. Morphology 4-5

§ Morphology (1)– Fig. x Location right above the kidneys 2.Gross Anatomy and Histology– A.Outer cortex-- > 3/4 of adrenal mass –Divided into 3 zones and produces steroids; –Zona glomerulosa– aldosterone –Zona fasciculata– cortisol and androgens –Zona reticularis– cortisol and androgens B.Inner medulla 1/4 –A modified sympathetic ganglion, releases epinephrine and norepinephrine 4-6

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4.3. Adrenal cortex 4-9

§ Adrenal Cortex 1.Adrenal cortex is essential for maintenance of life. 2.Addisons disease– pathological destruction or surgical removal of the adrenal cortex– death within 1-2 weeks 3.Why? 3 categories of hormones: Fig. 4.2– ALL come from cholesterol –Mineralocorticoids– essential to maintain sodium and potassium balance– Aldosterone + deoxycorticosterone (DOC) –Glucocorticoids– include cortisol and corticosterone– maintain CHO reserves –Androgens– on puberty and fetal life 4-10

The principal adrenal steroid hormones 4-11

4.3A. Adrenocortical hormones 4-12

§ adrenocortical hormones 1.All the adrenal steroids are from cholesterol– same as other steroids including... 2.Naming steroids –Fully saturated 21-carbon molecule is called pregnane –Delta– location of double bond(s) and -ane changes to -ene or to –diene –Presence of a hydroxyl group (-ol) –Presence of a keto group (-one) –Fig

All three reactions are catalyzed by a single enzyme, cytochrome P450 SCC. Pregnenolone– an important molecule for other adrenal hormones 4-14

§ Adrenal Cortex (1) 1.Pregnenolone and progesterone (21 Carbons) is the common precursor of all steroid hormones produced by the adrenals or the gonads (Fig. 4.4) 4-15

Z. glomerulosa Z. fasciculata Z. reticularis; 19 carbons Z. glomerulosa & reticularis Biosynthesis of adrenal cortical H. 4-16

§ Adrenal Cortex (2) 2.A hydroxyl group at carbon 11 is found in all glucocorticoids–that is corticosterone and cortisol 3.Corticosterone is the major glucocorticoid in the rat but is of only secondary importance in humans 4.Cortisol is the most potent of the naturally occurring glucocorticoids in humans 5.Corticosterone is a precursor of aldosterone (a major mineralocorticoid) Fig

Z. glomerulosa Z. fasciculata Z. reticularis; 19 carbons Z. glomerulosa & reticularis Biosynthesis of adrenal cortical H. Glucocorticoids A major mineralocorticoid 4-18

§ Adrenal Cortex (3) 6.Male hormones--Steroids in the 19-carbon series usually have androgenic (male hormone) activity) 7.Locations--This above reaction normally occurs only after puberty, and is confined to the cells of the zona reticularis (Fig. 4.4) 8.Female hormones--19-carbon steroids are precursors of the estrogens (female hormones; 18-carbon)unsaturated A ring due to aromatization (loss of the methyl carbon at position 19). This reaction happens in ovary and placenta normally. Fig

Z. glomerulosa Z. fasciculata Z. reticularis; 19 carbons– Male steroid hormones Z. glomerulosa & reticularis Biosynthesis of adrenal cortical H. Glucocorticoids A major mineralocorticoid 4-20

Principal 18-carbon estrogens A 4-21

4.3B. Control of adrenal cortical hormone synthesis 4-22

§ Effects of ACTH 1.ACTH has impact on z. fasciculata and reticularis but not glomerulosa 2.Through G-protein-coupled mem receptor 3.Increases cholesterol availability– in the cell and specifically also in mitochondria 4.(specifically on androgens)--ACTH is the only hormone known to control synthesis of the adrenal androgens (dehydroepiandrosterone sulfate; DHEAS) 5.Adrenarche– Beginning of increased secretion of adrenal hormones at puberty (another similar term: menarche) Fig

Steroid synthesis by ACTH in Z. Fasciculata 4-24

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§ control of aldosterone synthesis 1.Location– in zona glomerulosa 2.ACTH is NOT an important regulator of aldosterone production in most species 3.Angiotensin II (from Angiotensinogen, from liver) regulates the production of aldosterone How? 4.(first messenger-receptor)Angiotensin II binds with specific G-protein-coupled receptor 5.(second messengers)– IP3 and calcium to promote the formation of pregnenolone from cholesterol Fig. x

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4-28 Angiotensin II

§ control of aldosterone synthesis Impact by three ions-- 6.(K + )-- Cells of the zona glomerulosa are very sensitive to changes in potassium in the ECF; increased K+ (ECF) stimulates production of aldosterone 7.(Na + )-- Aldosterone is the principal regulator of body sodium content 8.(Ca +2 )-- Intracellular calcium also stimulates the synthesis of aldosterone. 4-29

4.3C. Adrenal steroid hormones in blood 4-30

§ plasma binding proteins 1.CBG, corticosteroid binding globulin (or called transcortin), and albumin 2.Both are produced in the liver 3.CBG has a single steroid hormone binding site whose affinity for cortisol is 20 times higher than for aldosterone 4.About 95% of the cortisol and about 60% of the aldosterone in blood are bound to protein 4-31

4.4A. Physiology of the mineralocorticoids (Mainly aldosterone & deoxycorticosterone, also others; See Fig. 4.2) 4-32

The principal adrenal steroid hormones 4-33

§ Introduction 1.Aldosterone is the most important mineralocorticoid 2.Aldosterones physiology and life-threatening changes: A.Reabsorption of sodium is decreased and fall of sodium in blood (hyponatremia) B.An accompanying loss of water C.Resulting decrease in blood volume called hypovolemia. D.Locations of these effects– the kidney is the most important; also in the sweat glands, the colon, and the salivary glands 4-34

§ Aldosterone on the kidney-A 1.Increased potassium excretion 2.Sodium retention (decrease in urinary sodium)– The above two ions are not tightly coupled and sodium is not simply exchanged for potassium 3.Increase in body weight due to fluid retention Fig

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§ Aldosterone on the kidney-B 1.Aldosterone sensitive cells called principal cells found in the nephrons– specifically in the connecting tubule and the cortical portion of the collecting duct 2.Details –Sodium (two-step transfer)– (A) enters the principal cells via sodium channels; (B) and is pumped out by sodium-potassium ATPase –Potassium– ROMK (renal outer medullary K+) channels on both sides of principal cells –Fig. 9.2; Fig

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In principal cells of cortical colleting duct lumenInterstitium 4-39

§ Aldosterone on the kidney-C 1.On principal cells– A.after 30 minutes– resulting in prolonged half-life of ENaC B.Later effects--Mainly by increasing the expression of proteins associated of sodium transport –Fig. 4.14B & 4.14C 4-40

In principal cells aldosterone effects after 30 min. delay SGK1– serum glucocorticoid dependent kinase 1 ENaC--Epithelial sodium channel Mainly by prolonging the half-life of ENaC 4-41

In principal cells– later effects of aldosterone Mainly by increasing the expression of proteins associated of sodium transport. 4-42

§ Aldosterone on the kidney-D 1.Aldosterone also targets intercalated cells found in the nephrons– specifically in the distal nephron and collecting duct –Fig. 9.2; Fig. 4.14D 4-43

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Mainly by promoting the secretion of protons (hydrogenions) in luminal membranes AR– Aldosterone receptors on the cell surface 4-45

4.4B– Regulation of aldosterone secretion 4-46

§ Aldosterone secretion and function 1.Stimuli for aldosterone secretion: –Primary-- Angiotensin II –Also by ACTH and high conc. of potassium 2.Angiotensin II is regulated by renin from the kidney (glomerular arterioles) –Principal stimulus for renin secretion is a decrease in the blood (or vascular) volume 3.Principal physiology of aldosterone: –Defend the blood volume by reabsorbing sodium & water from the kidney –X + Fig

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Monitored variables– A-- blood volume B-- plasma potassium conc. 4-49

4.5– Physiology of the glucocorticoids 4-50

§ Glucocorticoids 1.Physiology roles can be summarized as Coping with adversity 2.Major role-- in maintaining carbohydrate reserves 3.Do have many other functions (Table 4.2); every tissue of the body is affected by glucocorticoids 4-51

§ Major effects on energy metabolism by the glucocorticoids (cortisol etc.) 1.CHO A.Decrease utilization of glucose B.Promote hepatic gluconeogenesis (produce sugar from nonglucose precursors) C.Defend against hypoglycemia D.Promote glycogen storage in liver and muscle 2.Proteins--Inhibit protein synthesis and promote proteolysis (rapid breakdown of stored protein in muscle tissues etc.) 3.Lipids-- Increase lipolysis in adipose tissue Fig

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