title: Comparative evaluation of nonylphenol isomers on steroidogenesis of rat Leydig Cells.
abstract: Nonylphenol (NP) has been proven to be one of the most investigated xenohormones interacting with the estrogen receptor. Technical nonylphenol (t-NP) contains at least 20 para-substituted isomers. It has been shown that NP isomers vary in their estrogenic potency. So the use of mixtures or impure substances can lead to misinterpretations and unsatisfying conclusions. In the present study, experiments were performed to examine effects of NP isomers on steroidogenesis of rat Leydig cells. Primary cultured Leydig cells were exposed to NP isomers (p33-NP, p262-NP, p353-NP, p363-NP) at the optimized inhibitory concentration 5μmol/L for 6h. NP isomers showed various degrees of inhibition of testosterone biosynthesis, with p363-NP leading to the most significant decrease and others sharing the similar efficacy. The expression of 3b-HSD, Cyp11a1, Star and the apoptosis of Leydig cells were further measured to investigate the underlying mechanisms. We demonstrated that NP isomers can affect the steroidogenesis of rat Leydig cells, at least in part, through their influence on gene expression and cell apoptosis, but varied in their individual degree. However, the final results were not completely coincident with their estrogenic potency tested in vitro, which implies that effects of NP isomers on steroidogenesis appear to be mediated through some other underlying mechanisms besides their various estrogenic potency.
authors: Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China.
authors: Feng
authors: F
authors: Ying
authors: Chao
authors: C
authors: Ding
authors: Rong
authors: R
authors: Ge
authors: Xueting
authors: X
authors: Wang
authors: Fangjie
authors: F
authors: Li
authors: Yangheng
authors: Y
authors: Zhang
authors: Qiuqiong
authors: Q
authors: Zeng
authors: Bin
authors: B
authors: Yu
authors: Rong
authors: R
authors: Ji
authors: Xiaodong
authors: X
authors: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004965:Estrogen Antagonists / Q000737:chemistry / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D020287:In Situ Nick-End Labeling / Q000379:methods; D007536:Isomerism; D007985:Leydig Cells / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000633:toxicity*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013251:Steroid Isomerases / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D004965:Estrogen Antagonists; D009097:Multienzyme Complexes; D010636:Phenols; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; C025256:nonylphenol; D011375:Progesterone Reductase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D013251:Steroid Isomerases