The adrenal cortex is the outer layer of the adrenal gland. It works as a steroid-producing factory: it takes cholesterol and builds three hormone families from it, and each family has its own controlling signal and its own actions. Understanding how the gland is built explains a great deal about how its hormones behave.
What is the adrenal cortex and where does it sit?
The adrenal glands are a pair of endocrine glands sitting on top of the kidneys, which is why they are also called the suprarenal glands. Each gland weighs about 4 to 6 grams. The cortex is the outer layer of each one.
How does blood reach and leave the gland?
A gland whose hormones act on the whole body needs a rich blood supply, and the path the blood takes inside it matters. Arterial blood reaches the gland through several small arteries. These open into a capillary network beneath the capsule, and the capillaries run inward through the cortex towards the medulla. So the cortical cells are bathed by blood flowing from the outside inward, and the cortex is reached before the medulla.
Venous blood leaves the gland by a single central vein. The two sides differ. The right gland lies close to the inferior vena cava, and the right adrenal vein drains directly into it. The left gland lies farther away, and the left adrenal vein drains into the left renal vein.
What are the three zones and what does each make?
Blood passes through a cortex that is arranged as three concentric zones. Each zone produces a different class of steroid hormone:
- Zona glomerulosa, the outermost zone, produces the mineralocorticoid aldosterone.
- Zona fasciculata, the middle zone, produces the glucocorticoid cortisol.
- Zona reticularis, the innermost zone, produces adrenal androgen precursors.
A textbook mnemonic for the order from outside in is salt, sugar and sex.
Why does each zone make only its own hormone?
The layers all start from the same cholesterol, so the division of labour between them follows from the enzymes each one expresses. A steroid pathway can only be built from the enzymes a cell carries, so each cell can finish only the part of the pathway its enzymes allow.
There are two enzyme gates. The first is 17α-hydroxylase (CYP17A1), the enzyme needed to enter the cortisol and androgen routes. The zona glomerulosa lacks it, so the glomerulosa is confined to the mineralocorticoid pathway. The zona fasciculata and the zona reticularis express CYP17A1, so they can make cortisol and androgens.
The second gate is aldosterone synthase (CYP11B2), which performs the final steps of aldosterone synthesis. The fasciculata and the reticularis lack it, and only the zona glomerulosa expresses it. So the two deeper zones cannot finish aldosterone.
This single enzyme partition is the reason too little aldosterone and too little cortisol can occur independently. Because the two outputs pass through separate enzyme gates, loss of one enzyme can remove one family’s output while leaving the other intact.
What do the three hormone families do?
Each zone makes its own hormone class, so the products reach different targets and do different work.
Aldosterone
Aldosterone is the main mineralocorticoid. It acts on the distal nephron, where it increases sodium reabsorption and increases potassium excretion. A proposed route is more sodium channels and sodium-potassium pumps in the principal cells of the distal nephron, which is how more sodium goes into the body and more potassium goes out. Water follows sodium, so aldosterone is the body’s main regulator of extracellular fluid volume. Through extracellular fluid volume, it regulates blood pressure.
Cortisol
Cortisol is the main glucocorticoid, and it is central to the response to stress. Raising the blood glucose fits that role, and cortisol does this in two ways. It promotes gluconeogenesis, the making of glucose from non-carbohydrate sources. It also limits glucose use in some tissues. Cortisol also maintains the responsiveness of blood vessels to catecholamines, so it helps keep blood pressure up. And it suppresses immune and inflammatory responses.
Adrenal androgen precursors
The precursors are chiefly DHEA, DHEAS (the sulfated form of DHEA) and androstenedione. On their own they are weak androgens. They are released into the blood and converted in peripheral tissues, including the gonads, into more potent androgens and into estrogens. So they contribute to the androgen and estrogen economy of the body outside the gonads.
What controls each family?
Aldosterone and cortisol are each governed by their own controlling signal. If cortisol and aldosterone each have their own signal, what tells the cortex to make more cortisol, and what tells it to stop?