Progress on endocrine disruptors affecting testicular 3β-hydroxysteroid dehydrogenase and their mechanism of action
3β-hydroxysteroid dehydrogenase(3β-HSD)is a steroidogenic enzyme that catalyzes the conversion of 3β-hydroxysteroids to 3-ketosteroids.Two different subtypes of human 3β-HSD,HSD3B1 and HSD3B2,have been cloned,with HSD3B2 primarily expressed in the testes.HSD3B2 exhibits 3β-HSD2 activity and is a dual-substrate enzyme that binds with co-factors NAD+and 3β-steroids.Many endocrine disruptors,including industrial compounds(phthalates,bisphenols,perfluoroalkyl substances,and benzophenones),pesticides and fungicides(organochlorine pesticides and organotins),food additives(butylated hydroxyanisole,resveratrol,gossypol,flavonoids and isoflavonoids,curcuminoids,and chalcones),and drugs(etomidate,mifepristone,and ketoconazole)inhibit testicular 3β-HSD,potentially interfering with androgen synthesis.In this review,we summarized the unique testicular subtypes of 3β-HSD,their genes,chemistry,subcellularity,location,and the endocrine disruptors that directly inhibit testicular 3β-HSD and their modes of inhibition,to provide reference for clinical research on androgen regulation methods and the development of androgen-targeted drugs.
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