Human placental 3β-hydroxysteroid dehydrogenase/steroid Δ5, 4-isomerase 1: Identity, regulation and environmental inhibitors. (1st September 2019)

• Record Type: Journal Article
• Authors: Zhu, Qiqi; Pan, Peipei; Chen, Xiuxiu; Wang, Yiyan; Zhang, Song; Mo, Jiaying; Li, Xiaoheng; Ge, Ren-Shan
• Is Part Of: Toxicology. Volume 425(2019)
• Publication Date: 2019-09-01
• Subjects: 3β-hydroxysteroid dehydrogenase/steroid Δ5 -- 4-isomerase 1 -- Pregnenolone -- Progesterone -- Steroidogenesis -- Placenta -- Inhibitors; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2019.152253
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: HSD3B1 catalyzes 3β-dehydrogenation and Δ5, 4-isomeration of 3β-hydroxysteroids. HSD3B1 is critical for progesterone synthesis. HSD3B1 expression is controlled by transcription factors and epigenetics. There is a SAR difference for phthalates in the inhibition of HSD3B1. 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.