Physiologic Course of Female Reproductive Function: A Molecular Look into the Prologue of Life

Figure 5

Steroidogenesis pathways and regulation in the adrenal zona reticularis. 3βHSD2: 3β-hydroxysteroid dehydrogenase 2; CYP11A1: cholesterol side-chain cleavage enzyme; CYP17: 17α-hydroxylase/17,20 lyase; DHEA: dehydroepiandrosterone; DHEAS: dehydroepiandrosterone sulfate; StAR: Acute Steroidogenic Regulatory Protein. After CYP11A1 acts on cholesterol, pregnenolone may undergo both functions of CYP17 (17α-hydroxylation and 17,20-lyation, the latter with cytochrome b₅ as a cofactor), rendering DHEA as a product. DHEA synthesis is favored in the zona reticularis because the 17,20-lyase function acts preferentially on Δ⁵ steroids, whose production is potentiated in adrenarche due to 3βHSD2 underexpression. Additionally, upregulated SULT2A1 expression augments DHEA sulfonation, preventing conversion to other metabolites. DHEAS is secreted and reconverted to DHEA by sulfatases in peripheral tissues, where it also undergoes type 5α-reductase catalysis and then exerts its effects.