Synthesis of adrenocortical hormones

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Synthesis of adrenocortical hormones

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An experiment is carried out on the adrenal cortex of mice to determine the enzymes involved in the synthesis of adrenocortical hormones. In the experiment, an enzyme called 11-B hydroxylase was inhibited in the zona glomerulosa of the adrenal cortex. Which of the following steps is most likely to be disrupted as a result of this?  

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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.

Summary

Adrenocortical hormones are synthesized in the adrenal cortex, part of the adrenal glands located above the kidneys. The hormones are synthesized from cholesterol by a series of biochemical reactions catalyzed by enzymes. The first step is the conversion of cholesterol to pregnenolone, then pregnenolone is converted to progesterone, androgens, and glucocorticoids. Further modifications of these molecules give rise to the different adrenocortical hormones, including aldosterone, cortisol, and androstenedione.

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)
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