Hormones of the Adrenal Cortex
Objectives
Name the hormones synthesized in and secreted from adrenal
cortex
List the steps of synthesis of adrenal cortical hormones writing
the precursors and the main enzymes involved
Describe the mechanisms of storage, transport , degradation
and excretion of each of the adrenal cortical hormones.
Explain the metabolic functions of adrenocorticosteroids
References
Harper’s Biochemistry 25th and 26th eds.
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Adrenal Glands
The outer part is called the adrenal cortex, which produces many
different hormones called corticosteroids. This includes 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, increase the blood pressure and heart rate during times of
stress.
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Adrenal Glands
BACK
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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 most important GC in humans.
Androgens:
The zona reticularis and fasciculata produce significant
amounts
of
androgen
precursor
DHEA
(dehydroepiandrosterone) and androstenedione (both
19 carbon).
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Synthesis of Adrenocortical Hormones
• Made from cholesterol taken from LDLs in the blood and stored in
adrenocortical cells
• Adrenocortical cells stimulated by ACTH or cAMP.
Cholesterol
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Synthesis of Adrenocortical Hormones
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Synthesis of Adrenocortical Hormones
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Synthesis of Adrenocortical Hormones
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Storage and secretion
• Little (if any) storage of steroid hormones , directly go into
circulation as and when they are produced
• Cortisol release follows the diurnal rhythm of ACTH release.
Highest levels in the morning shortly after awakening and
lowest in the evening and early morning.
Plasma Transport
•
•
•
•
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 CBG and has a half life of 1.5 - 2 hrs. 8-10% Cortisol
is free.
• Progesterone and deoxycorticosterone also bind CBG strongly.
• Corticosterone binds CBG with less affinity.
• Aldosterone does not have a specific protein but binds weekly
with albumin
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Degradation and Excretion
• Glucocorticoids: Cortisol, Cortisone and 11-deoxycortosol are
reduced by NADPH dependant enzymes and conjugated with
either glucoronate or sulfate which render them water soluble.
About 70% of the conjugated steroids are excreted in the urine ,
20% in feces and rest exit through the skin.
• Mineralocorticoids: Aldosterone is very rapidly cleared from
the plasma by liver because it lacks a specific protein carrier. It is
converted to tetrahydroaldosterone 3-glucoronide which is
excreted in urine.
• 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.
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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.
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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.
• Other biochemical functions:
•
•
•
•
Suppress immune response in high doses (esp. cortisol)
Modulate response of catecholamines
Increase the production of gastric HCl and pepsinogen
Inhibit the bone formation- increases the risk of osteoporosis.
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Hormones of the Adrenal Cortex
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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 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 mineral
deposition and bone growth.
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Metabolic functions of adrenocorticosteroids
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 transport proteins (pumps) which
facilitate Na and water movement across cell membranes.
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Hormones of the Adrenal Cortex
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