Mutation of HSD3B2 Gene and Fate of Dehydroepiandrosterone

BAQUEDANO M.S.; GUERCIO G; COSTANZO M; MARINO R; RIVAROLA MA,; BELGOROSKY A

VITAMINS AND HORMONES SERIES

ELSEVIER ACADEMIC PRESS INC

Lugar: Burlington, MA, Estados Unidos; Año: 2018

0083-6729

3βHSD2 enzyme is crucial for adrenal and gonad steroid biosynthesis. In enzymedeficiency states, due to recessive loss-of-function HSD3B2 mutations, steroid fluxis altered and clinical manifestations result. Deficiency of 3βHSD2 activity in theadrenals precludes normal aldosterone and cortisol synthesis and the alternative backdoorand 11‑oxygenated C19 steroid pathways and the flooding of cortisol precursorsalong the Δ5 pathway with a marked rise in DHEA and DHEAS production. In gonads,it precludes normal T and estrogen synthesis. Here, we review androgen-dependentmale differentiation of the external genitalia in humans and link this to femaledevelopment and steroidogenesis in the developing adrenal cortex. The molecularmechanisms governing postnatal adrenal cortex zonation and ZR development werealso revised. This chapter will review relevant clinical, hormonal, and genetic aspects of 3βHSD2 deficiency with emphasis on the significance of alternate fates encounteredby steroid hormone precursors in the adrenal gland and gonads. Our currentknowledge of the process of steroidogenesis and steroid action is derived from pathologicalconditions. In humans the 3βHSD2 deficiency represents a model of naturethat reinforces our knowledge about the role of the steroidogenic alternative pathwayin sex differentiation in both sexes. However, the physiological role of the high serumDHEAS levels in fetal life as well as after adrenarche remains to be elucidated.