Chapter 4-Adrenal Glands
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Ch. 4-- Study Guide
1. 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.
2. Comprehend Terminology (the text in
bold/italic)
3. Study and understand the text and
corresponding figures.
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4.1. Introduction
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§ 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 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
1. 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
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4.3. Adrenal cortex
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§ Adrenal Cortex
1. Adrenal cortex is essential for maintenance of
life.
2. Addison’s 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
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The principal adrenal steroid hormones
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4.3A. Adrenocortical
hormones
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§ 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. 4.3
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All three reactions are catalyzed by a single enzyme,
cytochrome P450SCC. Pregnenolone– an important
molecule for other adrenal hormones
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§ 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)
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Z. glomerulosa & reticularis
Biosynthesis of adrenal cortical H.
Z. reticularis;
19 carbons
Z. fasciculata
Z. glomerulosa
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§ 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. 4.4
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Z. glomerulosa & reticularis
Biosynthesis of adrenal cortical H.
Z. reticularis;
19 carbons
Glucocorticoids
Z. fasciculata
Z. glomerulosa
A major mineralocorticoid
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§ 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.
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Fig. 4.5
Z. glomerulosa & reticularis
Biosynthesis of adrenal cortical H.
Z. reticularis;
19 carbons–
Male steroid
hormones
Glucocorticoids
Z. fasciculata
Z. glomerulosa
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
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)
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Fig. 4.6 + 4.7
Steroid synthesis by ACTH in Z. Fasciculata
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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 + 4.8
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Angiotensin II
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§ 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.
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4.3C. Adrenal steroid
hormones in blood
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§ 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
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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
1. Aldosterone is the most important
mineralocorticoid
2. Aldosterone’s 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
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§ 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. 4.13
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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. 4.14
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In principal cells
of cortical
colleting duct
Interstitium
lumen
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§ 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
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In principal
cells—
aldosterone
effects after 30
min. delay
Mainly by prolonging
the half-life of ENaC
SGK1– serum
glucocorticoid
dependent kinase 1
ENaC--Epithelial
sodium channel
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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
1. 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 membranes
AR– Aldosterone
receptors on the cell
surface
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4.4B– Regulation of
aldosterone secretion
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§ 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. 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
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
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§ 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. 4.16
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