| Objective:Bisphenol A (BPA) is a kind of environmental endocrine disruptors(EEDs) which affects femal reproductive health. In this paper, weinvestigated the effect of BPA on testosterone production and expressionof P450c17a, P450scc and StAR genes in theca-interstitial cells of ratsand the effect of BPA on progesterone, estradiol production andexpression of P450arom, P450scc and Steroid Acute Regulator (STAR)genes in granulose cells of rats. The aim of this study was to demonstratethe mechanism of BPA in hormone production of women reproductionsystem and the possible pathway relating to growth and development ofwomen reproduction system of these environmental chemicals.Methods:The theca-interstitial cells and the granulose cells were isolatedfrom rat ovarian and cultured with MCcoy'5A medium, respectively. 72 hlater,, cells were treated with various concentrations of BPA (0, 10-7, 10-6,10-5, 10-4 M) and cultured for 48 h. Then the supematant was collectedand testosterone level in theca-interstitial cells medium and progesterone,estradiol level in granulose cells medium were detected with highlysensitive RIA. Gene expression of two key enzymes related with androgen production, P450c17a, P450scc and Steroid Acute Regulator(STAR) in the cultured theca-interstitial cells, as well asP450arom, P450scc, and StAR in the cultured granulose cells wereanalized by real-time RT-PCR.Results:BPA can affect the androgen production and secretion of primarilycultured theca-interstitial cells, testosterone levels in medium risedsignificantly (p＜0.05) after BPA treatment and were dose dependent. Thegene expression of the enzymes related with testosterone synthesisincreased significantly after BPA treatment. (p＜0.05 when 10-4M BPAwas used). StAR expression was also raised by BPA treatment in thecultured cells. BPA can affect the progesterone, estradiol production andsecretion of primarily cultured granulose cells. Progesterone levels inmedium rised side by BPA concentration's increase(p＜0.05), but aunexpectedly decline at 10-4 M group, (p＜0.01) after BPA treatment atdifferent concentration. However, estradiol level were decreased atconcentrations from 10-7 M to 10-4 M (p＜0.01). The gene expression ofthe enzymes related with progesterone, estradiol synthesis: Significantinhibitory effects on the expression of P450arom mRNA were observed.The expression of P450Scc mRNA were increased by BPA at 10-7 M and10-5 M, but unexpectedly decreased at 10-4 M, which was also the casefor progesterone. StAR mRNA in granulose cells were increased at different level.Conclusions:Bisphonel A can directly work on the theca-interstitial cells andgranulose cells: increased testosterone production and secretion byinducing expression of enzyme genes, P450c17a and P450Scc, whichrelated with androgen production. The key regulator of steroidogenesis,StAR was also induced high expression. Also, BPA can interactedprogesterone, estradiol synthesis by inducing expression of enzyme genes,P450arom and P450Scc and the key regulator of steroidogenesis-StAR.Exposed to BPA, the normal function of reproduction endocrine systemmay be disordered and deduced some endocrine disease. Partly resultedfrom influenced mRNA expression of steroridogenesis enzymes, thenomal hormone of ovarian synthesis were subjected, thus the nomalregulatory mechanism of HPO axile were disordered.
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