Chapter 4-Adrenal Glands - PowerPoint Presentation

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Chapter 4-Adrenal Glands

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Ch. 4-- Study Guide

Critically read (1) pages pp. 61-69 before

postsecretory metabolism of adrenal cortical hormones

section; (2) pp. 71-76 (physiology of the mineralocorticoids) before

Effects on water balance subsection.Comprehend Terminology (the text in bold/italic) Study and understand the text and corresponding figures.

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4.1. Introduction

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§ Introduction

Adrenal hormones:

required for maintenance of lifeWithout them, deranged electrolyte or CHO metabolism, hypoglycemic coma, and deathOuter cortex– three steroid hormones: mineralocorticoids, glucocorticoids, and androgensInner medulla—a component of the sympathetic nervous system

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4.2. Morphology

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§ Morphology (1)– Fig. x + 4.1

Location

— right above the kidneysGross Anatomy and Histology–Outer cortex-- > 3/4 of adrenal massDivided into 3 zones and produces steroids;Zona glomerulosa– aldosteroneZona fasciculata– cortisol and androgensZona reticularis– cortisol and androgensInner medulla -- @ 1/4

A modified sympathetic ganglion, releases epinephrine and norepinephrine

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4.3. Adrenal cortex

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§ Adrenal Cortex

Adrenal cortex is essential for maintenance of life.

Addison’s disease– pathological destruction or surgical removal of the adrenal cortex– death within 1-2 weeksWhy? 3 categories of hormones: Fig. 4.2– ALL come from cholesterolMineralocorticoids– essential to maintain sodium and potassium balance– Aldosterone + deoxycorticosterone (DOC)Glucocorticoids– include cortisol and corticosterone– maintain CHO reservesAndrogens– on puberty and fetal life

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The principal adrenal steroid hormones

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4.3A. Adrenocortical hormones

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§ adrenocortical hormones

All the adrenal steroids are from cholesterol– same as other steroids including . . .

Naming steroids—Fully saturated 21-carbon molecule is called pregnaneDelta– location of double bond(s) and -ane changes to -ene or to –dienePresence of a hydroxyl group (-ol)Presence of a keto group (-one)Fig. 4.3

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All three reactions are catalyzed by a single enzyme, cytochrome P450

SCC

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Pregnenolone– an important molecule for other adrenal hormones

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§ Adrenal Cortex (1)

Pregnenolone and progesterone

(21 Carbons) is the common precursor of all steroid hormones produced by the adrenals or the gonads (Fig. 4.4)

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Z. glomerulosa

Z. fasciculata

Z. reticularis; 19 carbons

Z. glomerulosa & reticularis

Biosynthesis of adrenal cortical H.

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§ Adrenal Cortex (2)

A hydroxyl group at carbon 11 is found in all

glucocorticoids–that is corticosterone and cortisolCorticosterone is the major glucocorticoid in the rat but is of only secondary importance in humansCortisol is the most potent of the naturally occurring glucocorticoids in humansCorticosterone is a precursor of aldosterone (a major mineralocorticoid)Fig. 4.4

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Z. glomerulosa

Z. fasciculata

Z. reticularis; 19 carbons

Z. glomerulosa & reticularis

Biosynthesis of adrenal cortical H.

Glucocorticoids

A major mineralocorticoid

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§ Adrenal Cortex (3)

Male hormones

--Steroids in the 19-carbon series usually have androgenic (male hormone) activity) Locations--This above reaction normally occurs only after puberty, and is confined to the cells of the zona reticularis (Fig. 4.4)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. 4.5

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Z. glomerulosa

Z. fasciculata

Z. reticularis; 19 carbons– Male steroid hormones

Z. glomerulosa & reticularis

Biosynthesis of adrenal cortical H.

Glucocorticoids

A major mineralocorticoid

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Principal 18-carbon estrogens

A

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4.3B. Control of adrenal cortical hormone synthesis

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§ Effects of ACTH

ACTH has impact on z. fasciculata and reticularis but not glomerulosa

Through G-protein-coupled mem receptorIncreases cholesterol availability– in the cell and specifically also in mitochondria(specifically on androgens)--ACTH is the only hormone known to control synthesis of the adrenal androgens (dehydroepiandrosterone sulfate; DHEAS)Adrenarche– Beginning of increased secretion of adrenal hormones at puberty (another similar term: menarche)

Fig. 4.6 + 4.7

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Steroid synthesis by ACTH in Z. Fasciculata

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§ control of aldosterone synthesis

Location– in

zona glomerulosaACTH is NOT an important regulator of aldosterone production in most speciesAngiotensin II (from Angiotensinogen, from liver) regulates the production of aldosteroneHow?(first messenger-receptor)—Angiotensin II binds with specific G-protein-coupled receptor(second messengers

)– IP3 and calcium

to promote the formation of pregnenolone from cholesterolFig. x + 4.8

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Angiotensin II

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§ control of aldosterone synthesis

Impact by three ions--

(K+)-- Cells of the zona glomerulosa are very sensitive to changes in potassium in the ECF; increased K+ (ECF) stimulates production of aldosterone(Na+)-- Aldosterone is the principal regulator of body sodium content(Ca+2)-- Intracellular calcium also stimulates the synthesis of aldosterone.

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4.3C. Adrenal steroid hormones in blood

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§ plasma binding proteins

CBG

, corticosteroid binding globulin (or called transcortin), and albuminBoth are produced in the liverCBG has a single steroid hormone binding site whose affinity for cortisol is 20 times higher than for aldosteroneAbout 95% of the cortisol and about 60% of the aldosterone in blood are bound to protein

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4.4A. Physiology of the mineralocorticoids (Mainly aldosterone &

deoxycorticosterone

, also others; See Fig. 4.2)

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The principal adrenal steroid hormones

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§ Introduction

Aldosterone is the most important mineralocorticoid

Aldosterone’s physiology and life-threatening changes: Reabsorption of sodium is decreased and fall of sodium in blood (hyponatremia)An accompanying loss of waterResulting decrease in blood volume called hypovolemia.Locations of these effects– the kidney is the most important; also in the sweat glands, the colon, and the salivary glands

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§ Aldosterone on the kidney-A

Increased potassium excretion

Sodium retention (decrease in urinary sodium)– The above two ions are not tightly coupled and sodium is not simply exchanged for potassiumIncrease in body weight due to fluid retention Fig. 4.13

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§ Aldosterone on the kidney-B

Aldosterone sensitive cells called

principal cells found in the nephrons– specifically in the connecting tubule and the cortical portion of the collecting duct 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 cellsFig. 9.2; Fig. 4.14

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In principal cells of cortical colleting duct

lumen

Interstitium

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§ Aldosterone on the kidney-C

On principal cells–

after 30 minutes– resulting in prolonged half-life of ENaCLater effects--Mainly by increasing the expression of proteins associated of sodium transportFig. 4.14B & 4.14C

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In principal cells—aldosterone effects after 30 min. delay

SGK1

– serum glucocorticoid dependent kinase 1ENaC--Epithelial sodium channel

Mainly by prolonging the half-life of ENaC

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In principal cells– later effects of aldosterone

Mainly by increasing the expression of proteins associated of sodium transport.

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§ Aldosterone on the kidney-D

Aldosterone also targets

intercalated cells found in the nephrons– specifically in the distal nephron and collecting duct Fig. 9.2; Fig. 4.14D

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Mainly by

promoting the secretion of protons (

hydrogenions) in luminal membranesAR– Aldosterone receptors on the cell surface

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4.4B– Regulation of aldosterone secretion

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§ Aldosterone secretion and function

Stimuli for aldosterone secretion:

Primary-- Angiotensin IIAlso by ACTH and high conc. of potassiumAngiotensin II is regulated by renin from the kidney (glomerular arterioles)Principal stimulus for renin secretion is a decrease in the blood (or vascular) volumePrincipal physiology of aldosterone:Defend the blood volume by reabsorbing sodium & water from the kidneyX + Fig. 4.15

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Monitored variables–

A--

blood volume B--plasma potassium conc.

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4.5– Physiology of the glucocorticoids

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§ Glucocorticoids

Physiology roles can be summarized as “Coping with adversity”

Major role-- in maintaining carbohydrate reservesDo have many other functions (Table 4.2); every tissue of the body is affected by glucocorticoids

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§ Major effects on energy metabolism by the glucocorticoids (cortisol etc.)

CHO—

Decrease utilization of glucosePromote hepatic gluconeogenesis (produce sugar from nonglucose precursors)Defend against hypoglycemiaPromote glycogen storage in liver and muscle Proteins--Inhibit protein synthesis and promote proteolysis (rapid breakdown of stored protein in muscle tissues etc.)Lipids-- Increase lipolysis in adipose tissue

Fig. 4.16

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