The hypothalamic-pituitary-adrenal (HPA) axis is involved in the production of glucocorticoids and adrenal androgens from the zona fasciculata and zona reticularis. Hypothalamic-Pituitary-Adrenal (HPA) Axis Although DHEA is predominantly made, some of it can be converted into androstenedione by 3ß-hydroxysteroid dehydrogenase in the reticularis. In the reticularis, 17-hydroxypregnenolone and 17-hydroxyprogesterone can be converted into DHEA and androstenedione by 17,20 lyase (17 alpha-hydroxylase). In the fasciculata, 17-alpha-hydroxylase converts pregnenolone and progesterone, which were synthesized in the glomerulosa, into 17-hydroxypregnenolone and 17-hydroxyprogesterone, respectively 3-beta-dehydrogenase converts 17-hydroxypregnenolone into 17-hydroxyprogesterone 21-hydroxylase converts 17-hydroxyprogesterone to 11-deoxycortisol and 11-beta-hydroxylase converts 11-deoxycortisol to cortisol, the predominant glucocorticoid. Aldosterone, corticosterone, and deoxycorticosterone all have mineralocorticoid activity with aldosterone being the predominant mineralocorticoid in man. Finally, aldosterone synthase, which is present only in the glomerulosa and is regulated by angiotensin II, converts corticosterone into aldosterone. Since the glomerulosa does not have 17 alpha-hydroxylase, pregnenolone can only be converted into progesterone via 3-beta-dehydrogenase 21-hydroxylase catalyzes conversion to 11-deoxycorticosterone 11-beta-hydroxylase catalyzes conversion to corticosterone. The downstream fate of pregnenolone will depend on the specific enzymes within that zone. Of note, ACTH induces steroidogenesis in all 3 zones by stimulating this rate-limiting enzyme.

CYP11A1 catalyzes the rate-limiting step of steroid hormone production, and it is expressed in all three layers of the adrenal cortex.

In the inner mitochondrial membrane, the cholesterol can then be converted to pregnenolone via CYP11A1 (cholesterol desmolase, or cholesterol side-chain cleavage, P450scc). Once cholesterol enters the cell, steroidogenic acute regulatory protein (StAR) regulates cholesterol transport from the outer mitochondrial membrane to the inner mitochondrial membrane. The zona glomerulosa produces mineralocorticoids, the zona fasciculata produces glucocorticoids, and the zona reticularis produces androgen precursors (mostly DHEA with some androstenedione). However, the specific steroid hormone produced differs in each layer because of zonal specific enzymes. Each layer produces steroid hormones from the precursor cholesterol. It has 3 distinct functional and histological zones: the zona glomerulosa (outermost layer), the zona fasciculata (middle layer), and the zona reticularis (innermost layer).

The adrenal cortex takes part in steroidogenesis, producing glucocorticoids, mineralocorticoids, and androgen precursors.

Adrenal hormone production