摘要
睾丸3β-羟基类固醇脱氢酶(3β-hydroxysteroid dehydrogenase,3β-HSD)是一种类固醇生成酶,催化3β-羟基类固醇转化为3-酮类固醇.目前已克隆了人类的两种不同亚型,HSD3B1和HSD3B2;其中,HSD3B2位于睾丸中,表达3β-HSD2.HSD3B2是一种双底物酶,可与辅因子NAD+和3β-类固醇结合.许多内分泌干扰物,包括工业化合物(邻苯二甲酸盐、双酚类、全氟烷基物质和二苯甲酮类)、杀虫剂和杀菌剂(有机氯杀虫剂和有机锡)、食品添加剂(丁基羟基苯甲醚、白藜芦醇、棉酚、黄酮和异黄酮、类姜黄素和查尔酮类)和药物(依托咪酯、甲羟孕酮和酮康唑)可抑制睾丸中3β-HSD的活性,可能干扰雄激素合成.本文总结了3β-HSD的独特睾丸亚型,其基因、化学、亚细胞、位置以及直接抑制睾丸3β-HSD的内分泌干扰物及其抑制模式,期望为临床研究雄激素调控方法及以雄激素为靶点的药物研发提供参考.
Abstract
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.
基金项目
温州市生殖与遗传学重点实验室资助(22HZSY0051)
NETL
NSTL
万方数据