Human placental 3β-hydroxysteroid dehydrogenase/steroid Δ5,4-isomerase 1: Identity, regulation and environmental inhibitors

Toxicology. 2019 Sep 1:425:152253. doi: 10.1016/j.tox.2019.152253. Epub 2019 Jul 25.

Abstract

Human placental 3β-hydroxysteroid dehydrogenase/steroid Δ5, 4-isomerase 1 (HSD3B1), a high-affinity type I enzyme, uses pregnenolone to make progesterone, which is critical for maintenance of pregnancy. HSD3B1 is located in the mitochondrion and the smooth endoplasmic reticulum of placental cells and is encoded by HSD3B1 gene. HSD3B1 contains GATA and TEF-5 regulatory elements. Many endocrine disruptors, including phthalates, methoxychlor and its metabolite, organotins, and gossypol directly inhibit placental HSD3B1 thus blocking progesterone production. In this review, we discuss the placental HSD3B1, its gene regulation, biochemistry, subcellular location, and inhibitors from the environment.

Keywords: 3β-hydroxysteroid dehydrogenase/steroid Δ5; 4-isomerase 1; Inhibitors; Placenta; Pregnenolone; Progesterone; Steroidogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Environmental Pollutants / adverse effects
  • Female
  • Gene Expression Regulation
  • Humans
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Placenta / drug effects
  • Placenta / enzymology*
  • Placenta / metabolism
  • Pregnancy
  • Progesterone Reductase / antagonists & inhibitors
  • Progesterone Reductase / chemistry
  • Progesterone Reductase / genetics
  • Progesterone Reductase / metabolism*
  • Steroid Isomerases / antagonists & inhibitors
  • Steroid Isomerases / chemistry
  • Steroid Isomerases / genetics
  • Steroid Isomerases / metabolism*

Substances

  • 3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase
  • Environmental Pollutants
  • Multienzyme Complexes
  • Progesterone Reductase
  • Steroid Isomerases