An onion with three layers
Look at the cortex under a microscope and you find three concentric zones, each a specialist. From outside to inside: the zona glomerulosa makes aldosterone; the broad middle zona fasciculata makes cortisol; and the deepest zona reticularis makes adrenal androgens like DHEA. That is the salt, sugar, sex sequence made literal — glomerulosa for salt, fasciculata for sugar, reticularis for sex.
From cholesterol to three destinations
Steroidogenesis — the building of steroids — always starts the same way. Cholesterol is shuttled into the mitochondrion and an enzyme snips it down to pregnenolone, the common ancestor of every adrenal steroid. From pregnenolone the path branches. Which branch a cell takes depends entirely on which enzymes that zone happens to carry.
The glomerulosa alone carries the final enzyme (aldosterone synthase) needed to finish aldosterone, but it lacks the enzyme to make androgens. The reticularis is the mirror image: it has the androgen-making enzymes but not aldosterone synthase. The fasciculata sits in the middle and channels everything toward cortisol. Same starting material, three outcomes — decided by enzyme inventory.
STEROIDOGENESIS (simplified branching)
CHOLESTEROL
│ (cut by side-chain enzyme, in mitochondrion)
▼
PREGNENOLONE ── the common ancestor
│
┌─────────┼───────────────┐
▼ ▼ ▼
glomerulosa fasciculata reticularis
│ │ │
▼ ▼ ▼
ALDOSTERONE CORTISOL DHEA / androgens
(salt) (sugar) (sex)
Key: each zone owns only some enzymes,
so each can finish only its own product.Why this layered design matters clinically
Because the zones share early steps but differ at the end, a block at one enzyme can dam the river and send the flow elsewhere. If the enzyme that makes cortisol is missing, precursors back up and spill into the androgen path — the core of congenital adrenal hyperplasia, which we meet later in this track. Understanding the plumbing is what makes those diseases make sense.