Adrenal Cortical Hormones

STEROID HORMONES

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The adrenal cortex has 3 different zones for the production of different classes of steroid hormones.

The smallest and outermost zona glomerulosa produces the C21 steroids, mineralocorticoids. They have effects on water & electrolyte balance.
The middle zone of the adrenal cortex, the zona fascicularis produces the glucocorticoids mainly; adrenal androgens and, estrogens to a lesser extent
The innermost zona reticularis produces the androgens (C19) & estrogens (C18)

Cholesterol is first acted upon by desmolase and a 6-carbon unit is cleaved off, forming the 21-Carbon steroid, Pregnenolone.
Pregnenolone is a common precursor for all the steroid hormones.
This is the rate limiting step for synthesis of all steroid hormones.
Adrenocorticotropic hormone (ACTH) stimulates this step.
Progesterone is the first steroid hormone formed from pregnenolone in two steps.
The β-hydroxyl group is converted to a keto group by a 3-beta-oldehydrogenase & the Δ5 double bond shifted to Δ4.
Progesterone is further converted into glucocorticoids, mineralocorticoids and sex steroids.
The major adrenal glucocorticoids are cortisol, cortisone and corticosterone.
The major mineralocorticoid is aldosterone, but 11-deoxycorticosterone and corticosterone also have significant mineralocorticoid activity.
These reactions are affected by hydroxylation.
These specific hydroxylases are mono-oxygenases. (All these enzymes are NADPH dependent).
The ACTH stimulates the synthesis of all steroid hormones by activating desmolase so that the availability of pregnenolone is increased.

Secretion of all adrenocortical hormones is under the control of ACTH.
The diurnal variation of secretion of cortisol (highest values early in the morning and minimum at night) parallels the pulsatile release of ACTH from anterior pituitary under the influence of CRF.
Cortisol exerts the negative feedback effect on ACTH secretion.
The ACTH also increases the secretion of aldosterone.
The level of aldosterone is also affected by position, highest values in upright posture and lowest while lying down.
All steroid hormones act through intracellular messengers and increase the rate of transcription.

Approximately 70% of cortisol in blood is bound to an alpha-1-globulin called Cortisol Binding Globulin (CBG) or Transcortin.
About 20% is bound to albumin and the rest is free, which is the biologically active fraction.
The half-life of cortisol is about 2 hours.
The steroid hormones are metabolized and inactivated by the liver.
The major processes are reduction & conjugation.
The C21 steroids are reduced to their tetrahydro derivatives, which are excreted as their glucuronides or sulfates in urine.
Mineralocorticoids (mainly aldosterone) increase sodium reabsorption from renal tubules, leading to sodium retention and resultant water retention.
It acts through Renin Angiotensin System.
The sodium potassium exchange at the renal tubules leads to increased potassium excretion.

Steroid hormones being lipid soluble can easily pass through the plasma membrane and enter the cytoplasm.
Here they combine with specific receptors and the HR complex, translocates to the nucleus (steroid hormones in general have nuclear receptors and act by regulation of gene expression).
They combine with steroid Hormone Response Elements (HRE) on DNA & regulate transcription of genes.
The proteins produced in response to the hormonal stimulation produce metabolic effects e.g. enzymes and transporters.