Synthesis of adrenocortical hormones

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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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The first step in the biosynthesis of adrenocortical hormones is converting cholesterol to pregnenolone by

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The adrenal glands are two glands that sit like a hat, one on top of each kidney. Each one has an inner layer called the medulla and an outer layer called the cortex.

The adrenal cortex is subdivided into three more layers, the zona glomerulosa, zona fasciculata, and the zona reticularis, which secrete steroid hormones under the control of adrenocorticotropic hormone, or ACTH.

Adrenocorticotropic hormone is released by the anterior pituitary gland and binds to receptors on adrenal cortex cells in all three layers, and makes them take up cholesterol from the blood.

ACTH also stimulates an enzyme called cholesterol desmolase inside these cells, which converts cholesterol to pregnenolone, which is the precursor to all of the adrenal cortex hormones.

The outermost layer is the zona glomerulosa, and it’s full of cells that make the hormone aldosterone.

The first step in aldosterone production is when an enzyme called 3 beta- hydroxysteroid dehydrogenase, (or 3 beta- HSD) turns pregnenolone into progesterone.

Next, progesterone is turned into 11 deoxycorticosterone (or 11- DOC) by the enzyme 21 hydroxylase. 11 deoxycorticosterone then gets turned into corticosterone by the enzyme 11 beta-hydroxylase.

And finally, corticosterone is turned into aldosterone by the enzyme aldosterone synthase. Whew! That’s like going through the washing machine twice.

Aldosterone synthase is stimulated by the hormone angiotensin II, which is produced in the lungs in response to decreased blood volume and blood pressure.

So the final result is aldosterone which belongs to a group of hormones called mineralocorticoids, which help regulate the body’s sodium concentration.

Aldosterone binds to receptors on the cells that line the distal tubules and collecting ducts in the kidney, and increases the expression of sodium/potassium ion pumps, which are on the basolateral surface of the cells - the side facing the blood.

These ion pumps drive potassium from the blood into the cells and from there it flows down its concentration gradient into the tubule to be excreted as urine.

At the same time, the pumps drive sodium in the opposite direction from the cell into the blood, which allows more sodium to flow from the tubule into the cell down its concentration gradient.

When Na+ is reabsorbed back into the blood, water also moves into the blood, and that increases blood volume and blood pressure.

Moving on from the zona glomerulosa, the middle layer of the adrenal cortex is the zona fasciculata, and the cells there make the hormone cortisol. This process starts when pregnenolone and progesterone move into the zona fasciculata.

The enzyme 17 alpha-hydroxylase turns pregnenolone into 17 alpha- hydroxypregnenolone and turns progesterone into 17 alpha hydroxyprogesterone.

17 alpha hydroxypregnenolone is then turned into 17 alpha hydroxyprogesterone by the enzyme 3 beta- hydroxysteroid dehydrogenase.

Then, all of the 17 alpha hydroxyprogesterone is turned into 11 deoxycortisol by the enzyme 21 hydroxylase.

11 deoxycortisol is finally turned into cortisol by the enzyme 11 beta-hydroxylase.

Sources
  1. "Medical Physiology" Elsevier (2016)
  2. "Physiology" Elsevier (2017)
  3. "Human Anatomy & Physiology" Pearson (2018)
  4. "Principles of Anatomy and Physiology" Wiley (2014)
  5. "ACTH protects against glucocorticoid-induced osteonecrosis of bone" Proceedings of the National Academy of Sciences (2010)
  6. "Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology" Pharmacological Reviews (2015)
  7. "Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function" American Journal of Physiology-Endocrinology and Metabolism (2011)
  8. "G Protein-Coupled Receptors: Extranuclear Mediators for the Non-Genomic Actions of Steroids" International Journal of Molecular Sciences (2014)