Effect of bisphenol A on human chorionic gonadotrophin-stimulated gene expression of cultured mouse Leydig tumour cells.
Endocrine disrupting chemicals (EDCs) have been reported to affect the reproductive system of various animal species. However, their specific effects and modes of action on gonadal function remain largely unclear. We studied the effects of a model EDC, bisphenol A (BPA), on human chorionic gonadotrophin (hCG)-stimulated global gene expression of cultured mouse Leydig tumour cells (mLTC-1). The time and dose of BPA exposure were set after semiquantitative (sq) RT-PCR analysis of response of candidate genes (StAR, Cyp 17 a1 and AR) to 3h at 10 microg/l hCG +/- 10(-5)M BPA. Affymetrix microarray analysis demonstrated > or =1.5-fold up-regulation of 8- and < or =1.5-fold down-regulated of 16 genes by BPA. Several of these genes were related to steroid/cholesterol metabolism/transport and cell cycle regulation. sqRT-PCR demonstrated induction of StAR expression by hCG stimulation and no effect of BPA. In conclusion, our results indicate that BPA has only subtle modulating effects on gene expression of gonadotrophin-stimulated mLTC-1 cells.
Takamiya
Minako
M
Cranfield Health, Cranfield University, Barton Road, Silsoe, Bedfordshire MK45 4DT, UK. m.takamiya.s01@Cranfield.ac.uk
Lambard
Sophie
S
Huhtaniemi
Ilpo T
IT
D000818:Animals; D001559:Benzhydryl Compounds; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000737:chemistry / Q000633:toxicity; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000633:toxicity; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007984:Leydig Cell Tumor / Q000235:genetics / Q000473:pathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010636:Phenols / Q000737:chemistry / Q000633:toxicity*; D010750:Phosphoproteins / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D006063:Chorionic Gonadotropin; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D010750:Phosphoproteins; D011944:Receptors, Androgen; D013254:Steroid 17-alpha-Hydroxylase; D000098682:Steroidogenic Acute Regulatory Protein; C501892:CYP17A1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds