Synthesis of adrenocortical hormones

Definitions & Key takeaways

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.

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Introduction0:00–0:22

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.

ACTH0:22–0:45

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.

Aldosterone0:45–2:17

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.

Cortisol2:17–4:05

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.
Cortisol is needed in times of emotional and physical stress like arguing with a friend or fleeing from a pack of raccoons.
In those situations, the hypothalamus—which is an almond-size structure in the brain, releases corticotropin-releasing hormone which acts on the pituitary gland, the pea-sized structure sitting just underneath the hypothalamus.
In response, the pituitary gland sends out adrenocorticotropic hormone, or ACTH, which travels through the blood to the zona fasciculata of the adrenal glands and signals cells there to release cortisol.
One of cortisol’s main jobs is to increase blood glucose levels by promoting gluconeogenesis in the liver. This is the formation of glucose from noncarbohydrate sources, like amino acids or free fatty acids.
Cortisol also increases the breakdown of proteins into amino acids in muscles as well as break down of fats into free fatty acids by adipose tissues, both of which provide the liver with more raw materials to work with.
The increase in glucose lets the body respond appropriately to those raccoons, or other stressors. Finally, there’s the innermost layer of the adrenal cortex which is the zona reticularis, and cells there make a group of sex hormones called androgens.

Androgens4:05–5:46

This process starts when 17 alpha hydroxypregnenolone and 17 alpha hydroxyprogesterone from the zona fasciculata move into the zona reticularis.
The enzyme 17, 20 lyase turns 17 alpha hydroxypregnenolone into dehydroepiandrosterone (or DHEA) and turns 17 hydroxyprogesterone into androstenedione.
Dehydroepiandrosterone can also be turned into androstenedione by the enzyme 3 beta- hydroxysteroid dehydrogenase. Then, androstenedione is turned into testosterone by the enzyme 17 beta hydroxysteroid dehydrogenase (or 17- beta HSD).
Alternatively you can also get testosterone by converting dehydroepiandrosterone to androstenediol first with the same enzyme, 17 beta- HSD, then using 3 beta hydroxysteroid dehydrogenase to get testosterone.
Finally, testosterone is turned into 17 beta-estradiol, also called estrogen, with the enzyme aromatase. The adrenal glands are involved in estrogen and testosterone production in both men and women, but the amount that the adrenals contribute is pretty small compared to testosterone formed by the testes, and estrogen formed by the ovaries.
So in men, testosterone is produced by both adrenal glands and testes, and is responsible for the development of male reproductive organs and secondary sex characteristics like voice changes and facial, underarm, and pubic hair.
Since women do not have testes, the small amount of testosterone produced by the adrenal glands is just enough to influence secondary sex characteristics like underarm and pubic hair.

Review5:46–6:17

Alright, as a quick recap… the adrenal cortex is divided into three layers; zona glomerulosa, zona fasciculata, and the zona reticularis, which secrete steroid hormones under the control of adrenocorticotropic hormone, released by the pituitary gland.
The adrenal cortex cells first convert cholesterol to pregnenolone using the enzyme cholesterol desmolase. Pregnenolone is then converted into aldosterone in the zona glomerulosa, cortisol in zona fasciculata; and testosterone and estrogen in zona reticularis.