US EPA

3350244 

Journal Article 

Comparison of the effects of dibutyl and monobutyl phthalates on the steroidogenesis of rat immature Leydig cells 

Li, L; Chen, X; Hu, G; Wang, S; Xu, R; Zhu, Q; Li, X; Wang, M; Lian, QQ; Ge, R 

2016 

Yes 

BioMed Research International
ISSN: 2314-6141 

2016 

1376526 

English 

27148549 

10.1155/2016/1376526 

WOS:000374936800001 

https://search.proquest.com/docview/1783860127?accountid=171501
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Dibutyl phthalate (DBP) is a widely used synthetic phthalic diester and monobutyl phthalate (MBP) is its main metabolite. DBP can be released into the environment and potentially disrupting mammalian male reproductive endocrine system. However, the potencies of DBP and MBP to inhibit Leydig cell steroidogenesis and their possible mechanisms are not clear. Immature Leydig cells isolated from rats were cultured with 0.05-50 μM DBP or MBP for 3 h in combination with testosterone synthesis regulator or intermediate. The concentrations of 5α-androstanediol and testosterone in the media were measured, and the mRNA levels of the androgen biosynthetic genes were detected by qPCR. The direct actions of DBP or MBP on CYP11A1, CYP17A1, SRD5A1, and AKR1C14 activities were measured. MBP inhibited androgen production by the immature Leydig cell at as low as 50 nM, while 50 μM was required for DBP to suppress its androgen production. MBP mainly downregulated Cyp11a1 and Hsd3b1 expression levels at 50 nM. However, 50 μM DBP downregulated Star, Hsd3b1, and Hsd17b3 expression levels and directly inhibited CYP11A1 and CYP17A1 activities. In conclusion, DBP is metabolized to more potent inhibitor MBP that downregulated the expression levels of some androgen biosynthetic enzymes. 

Medical Sciences; Androgens; Metabolism; Children & youth; Laboratory animals; Metabolites; Biosynthesis; Enzymes; Reproductive system; Cholesterol; Gene expression; Testosterone; Dehydrogenases; Endoplasmic reticulum