17hydroxylation

17-hydroxylation, often written 17α-hydroxylation, is a biochemical step in steroidogenesis in which a hydroxyl group is added to carbon 17 of the steroid nucleus, typically at the α-position. The reaction is carried out primarily by the enzyme CYP17A1, also known as cytochrome P450 17α-hydroxylase, which is located in the endoplasmic reticulum of steroidogenic cells in the adrenal cortex and gonads.

CYP17A1 possesses two catalytic activities. The 17α-hydroxylase activity adds an OH group at C17 to pregnenolone and progesterone, yielding 17α-hydroxypregnenolone and 17α-hydroxyprogesterone, respectively. The same enzyme also has 17,20-lyase activity, which can further convert these intermediates into dehydroepiandrosterone (DHEA) and androstenedione, enabling the production of glucocorticoids and sex steroids. The hydroxylated products are thus essential precursors in pathways leading to cortisol and androgens/estrogens.

Physiological significance is tied to regulation of adrenal and gonadal steroid outputs. The process is influenced by pituitary signals such as ACTH and LH/FSH, and it represents a rate-limiting step for certain branches of steroid biosynthesis. Clinically, deficiency of CYP17A1 causes congenital adrenal hyperplasia with reduced cortisol and androgens and often hypertension due to excess mineralocorticoids. Conversely, pharmacological inhibition of 17α-hydroxylase/17,20-lyase (for example, with certain anticancer drugs) can suppress androgen production.

In summary, 17-hydroxylation is a key early modification in the production of glucocorticoids and sex steroids, enabling downstream pathways that shape hormonal balance.