HORMONES OF THE ADRENAL

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
 SYNTHESIS OF
ADRENOCORTICAL HORMONES
 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).
 EPINEPHRINE AND NOREPINEPHRINE
(CATECHOLAMINES)

These compounds are synthesized from tyrosine in postganglionic nerve terminals

and in the adrenal medulla.
The catecholamines are stored in specific granula as complexes with ATP and
Mg++ and are released after arrival of neuronal signals, which are transmitted by
acetylcholine.
This takes place in physical and psychological stress situations.
The catecholamines act on several adrenergic receptor types, producing multiple
effects.
The expression of the biosynthetic enzymes tyrosine 3-monooxygenase
(hydroxylase) and dopamine b-hydroxylase is induced by neuronal signals, the
expression of phenylethanol amine N-methyltransferase by glucocorticoids.
Catecholamines, in turn, promote the synthesis of regulators of glucocorticoid
formation (CRH, ACTH), so that the result is an upregulating circuit

Biochemical Pathway, : an atlas of biochemistry and molecular biology / edited by Dietmar Schomburg, Gerhard Michal. -- 2nd ed.
 REGULATION OF
CATECHOLAMINE BIOSYNTHESIS

Biochemical Pathway, : an atlas of biochemistry and molecular biology / edited by Dietmar Schomburg, Gerhard Michal. -- 2nd ed.
 HYPOTHALAMO-PITUITARY-ADRENAL AXIS:

7 … 10 times a day, but increased during stress situations, the corticotropin releasing
hormone (CRH) is secreted from the hypothalamus and acts on the pituitary gland.

Here the proopio melanocortin (POMC) is synthesized and processed into corticotropin
(ACTH, stored in secretory granula), endorphins and a-, b- and g-melanocyte stimulating
hormone (MSH).

The CRH and the ACTH secretions occur spasmodically and follow the same rhythm.

Cortisol: In the adrenal cortex, ACTH activates (via cAMP/protein kinase A) the hydrolysis
of cholesterol esters and the de novo synthesis of cholesterol.

It also induces hydroxylases involved in the conversion of cholesterol to cortisol and

stimulates cortisol secretion. This steroid is bound to transcortin during transport in blood.

Biochemical Pathway, : an atlas of biochemistry and molecular biology / edited by Dietmar Schomburg, Gerhard Michal. -- 2nd ed.
 HYPOTHALAMO-PITUITARY-
ADRENAL AXIS:

Almost all cells of the organism are targets for cortisol action, where the hormone binds to
the internal cortisol receptor.
This induces transcription of genes coding for many catabolic enzymes in extrahepatic
tissues (as an antagonist to insulin) and for gluconeogenetic enzymes in liver.
It is also an immunosuppressor and a suppressor of inflammation.
The maximum of the wavelike diurnal cortisol secretion is in the morning, the minimum in
the evening, with additional spikes corresponding to the CRH/ACTH secretion.
Endorphins and related neuropeptides: Several endorphine isoforms and Met-enkephalin
are cleaved from POMC in the pituitary gland, but also in the stomach and intestine,
placenta, lung etc. Dynorphin and neoendorphins are cleaved from other precursors. They
act on opioid receptors and cause analgetic effects. They are also involved in body
temperature regulation.
Other cleavage products of POMC are melanotropins (MSH, melanocyte stimulating
hormones), which promote skin darkening in amphibia and fishes by activating tyrosinase,
which increases melanin synthesis.

Biochemical Pathway, : an atlas of biochemistry and molecular biology / edited by Dietmar Schomburg, Gerhard Michal. -- 2nd ed.
 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
 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.
 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.
HORMONES OF THE ADRENAL CORTEX
 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.
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.
HORMONES OF THE ADRENAL CORTEX