Overview

All adrenal steroids are made from cholesterol (mainly LDL-derived, stored as cholesteryl esters in lipid droplets). The rate-limiting step is the delivery of cholesterol to the inner mitochondrial membrane by the steroidogenic acute regulatory protein (StAR), where CYP11A1 (side-chain cleavage, "desmolase") makes pregnenolone. Each zone then expresses a different enzyme set, so each makes a different end product.

Zona glomerulosa (outer ≈10–15 %) lacks 17α-hydroxylase but has aldosterone synthase (CYP11B2): pregnenolone → progesterone → 11-deoxycorticosterone (21-hydroxylase) → corticosterone → aldosterone. It is controlled by angiotensin II and plasma K⁺ (ACTH has only a minor effect). Zona fasciculata (middle ≈75 %) has 17α-hydroxylase: pregnenolone → 17-OH-pregnenolone/17-OH-progesterone → 11-deoxycortisol (21-hydroxylase) → cortisol (11β-hydroxylase, CYP11B1); it is controlled by ACTH. Zona reticularis (inner ≈5–10 %) has strong 17,20-lyase activity → DHEA, DHEA-S and androstenedione; it is controlled by ACTH, switches on at adrenarche (≈6–8 years) and declines with age.

Because the zones share enzymes, an inherited block diverts precursors elsewhere — the basis of congenital adrenal hyperplasia.

Location: Outer part of each adrenal gland, beneath the capsule, surrounding the medulla.

Parts & subdivisions

Zona glomerulosa
Thin layer of small cells in rounded clusters (arcs) under the capsule — aldosterone ("salt").
Zona fasciculata
Thick layer of large pale lipid-laden cells ("spongiocytes") in radial cords between sinusoids — cortisol ("sugar").
Zona reticularis
Anastomosing network of smaller eosinophilic cells containing lipofuscin — DHEA, DHEA-S, androstenedione ("sex").

Anatomy

Histology: Capsule → glomerulosa (arched clusters) → fasciculata (long straight cords, vacuolated "foamy" cytoplasm from lipid) → reticularis (irregular network) → medulla. Abundant smooth ER and mitochondria with tubular cristae — features of steroid-secreting cells.

Function

Mineralocorticoid secretion (aldosterone) — Na⁺ retention, K⁺ and H⁺ excretion.
Glucocorticoid secretion (cortisol) — gluconeogenesis, stress response, anti-inflammatory and immunosuppressive effects.
Adrenal androgen secretion — pubic/axillary hair in females, adrenarche.

Regulation: Glomerulosa: angiotensin II (AT1, Gq) and hyperkalaemia (depolarisation, Ca²⁺ entry). Fasciculata and reticularis: ACTH via the MC2 receptor (Gs–cAMP), which acutely increases StAR activity and chronically causes hypertrophy; lack of ACTH causes atrophy of these zones (e.g. after long-term steroid therapy).

Clinical significance

Congenital adrenal hyperplasia (CAH)

Autosomal recessive defects of cortisol synthesis; low cortisol raises ACTH, which causes adrenal hyperplasia and shunts precursors into androgens. 21-hydroxylase deficiency (≈90–95 %): ↓ cortisol and aldosterone, ↑ 17-hydroxyprogesterone and androgens → salt-wasting crisis in neonates, virilisation and ambiguous genitalia in 46,XX infants, precocious pseudopuberty in boys. 11β-hydroxylase deficiency: virilisation with hypertension (11-deoxycorticosterone excess). 17α-hydroxylase deficiency: hypertension, hypokalaemia and absent sex steroids (sexual infantilism).

Cortical tumours

Adenomas may secrete cortisol (Cushing syndrome) or aldosterone (Conn syndrome); adrenocortical carcinoma is rare, large and often secretes several steroids (virilisation plus Cushing features).

Mnemonics

Zones and products

GFR — salt, sugar, sex: Glomerulosa → aldosterone; Fasciculata → cortisol; Reticularis → androgens.

Test yourself

Which zone of the adrenal cortex is primarily controlled by angiotensin II and serum potassium rather than ACTH?

Zona glomerulosa
Zona fasciculata
Zona reticularis
Adrenal medulla

Answer: Zona glomerulosa

Zona glomerulosa cells express aldosterone synthase (CYP11B2) and respond mainly to angiotensin II (AT1, Gq) and hyperkalaemia (depolarisation). ACTH has only a minor, transient effect, which is why pituitary failure spares aldosterone.