Which sterol serves as a precursor for steroid hormone synthesis?
Mammalian steroid hormone biosynthesis strictly begins cholesterol carbon skeleton source fundamental endocrine biochemistry regulation stress reproduction. Cholesterol imported via LDL receptor mediated endocytosis clathrin dependent or synthesized de novo via HMGCoA reductase in ER transferred mitochondria by steroidogenic acute regulatory protein StAR forming contact sites outer inner membrane requiring TSPO. Inner membrane P450 side chain cleavage CYP11A1 encoded fifteen q24 catalyzes three hydroxylations sequential oxygen NADPH adrenodoxin consuming producing twenty two R hydroxyl twenty alpha dihydroxycholesterol then cleaves C20 C22 side chain releasing six carbon isocaproaldehyde twenty one carbon pregnenolone first committed steroid intermediate moving cytosol. Pregnenolone exits ER where three beta hydroxysteroid dehydrogenase HSD3B2 CYP17A1 CYP21A2 CYP11B1 CYP11B2 CYP19A1 generate progesterone dehydroepiandrosterone androstenedione testosterone estradiol cortisol aldosterone mineralocorticoids. Ergosterol fungal sterol extra double bonds methyl not substrate mammalian CYP11A1, stigmasterol sitosterol plant sterols converted poorly. Cholesterol deficiency causes Smith Lemli Opitz DHCR7 lipoid congenital adrenal hyperplasia StAR illustrating essential endocrine role linking membrane lipid systemic physiology pharmacology statins endocrine disorders thoroughly examined physiology exams requiring pathway knowledge.
Ref: Payne AH & Hales DB, Endocrine Reviews 2004, Cholesterol as precursor pregnenolone steroid hormones biosynthesis.