期刊
MOLECULES
卷 16, 期 12, 页码 9983-10001出版社
MDPI
DOI: 10.3390/molecules16129983
关键词
endocrine disruptor; steroidogenic enzymes; steroidogenic inhibitors; Leydig cells; male reproduction
资金
- NSFC [81102150, 30871434]
- Science and Technology Planning Project of Guangdong Province [2010B05070000]
- Fundamental Research Funds for the Central Universities [21611508]
The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved in testosterone biosynthesis: Cholesterol side chain cleavage enzyme (CYP11A1) for the conversion of cholesterol into pregnenolone within the mitochondria, 3 beta-hydroxysteroid dehydrogenase (HSD3B), for the conversion of pregnenolone into progesterone, 17 alpha-hydroxylase/17,20-lyase (CYP17A1) for the conversion of progesterone into androstenedione and 17 beta-hydroxysteroid dehydrogenase (HSD17B3) for the formation of testosterone from androstenedione. Testosterone is also metabolically activated into more potent androgen dihydrotestosterone by two isoforms 5 alpha-reductase 1 (SRD5A1) and 2 (SRD5A2) in Leydig cells and peripheral tissues. Many endocrine disruptors act as antiandrogens via directly inhibiting one or more enzymes for testosterone biosynthesis and metabolic activation. These chemicals include industrial materials (perfluoroalkyl compounds, phthalates, bisphenol A and benzophenone) and pesticides/biocides (methoxychlor, organotins, 1,2-dibromo-3-chloropropane and prochloraz) and plant constituents (genistein and gossypol). This paper reviews these endocrine disruptors targeting steroidogenic enzymes.
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