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PARENT SESSION REPRODUCTIVE TOXICOLOGY Harborside C 7:30 AM-10:00 AM
(312) EFFECTS OF BISPHENOL-A AND OCTYLPHENOL ON THE EXPRESSION OF STEROIDOGENIC ENZYMES AND INHIBIN IN CULTURED MOUSE TESTICULAR CELLS.
Lee, Ho-Joon1, Kim, Suel-Kee1,3, An, Su-Yeon1, Kim, Myo-Kyung2, Ko, Duck-Sung2, Kim, Dong-Hoon2, Yoon, Yong-Dal3, 1 Department of Physiology, Taejon, Korea3 Department of Life Sceince, Seoul, Korea2 Eulji Research Institure, Seoul, Korea
ABSTRACT- Endocrine disrupting chemicals (EDCs) have been known to mimic or inhibit the function of the endogenous hormone in human or wildlife population, thereby may disturb the reproductive system. The normal development of male reproductive tract is depending upon endogenous hormone, testosterone. The biosynthesis of testosterone requires the expression of several enzymes, including cytochrome P450 cholesterol side-chain cleavage enzyme (CYPscc), 3 -hydroxysteroid dehydrogenase (3 -HSD) and cytochrome P450 17 -hydorxylase/C17,20-lyase (CYP17 ). Inhibin and activin produced mainly by Sertoli cell involves in negative feedback mechanisms which control the production of LH and FSH by acting on anterior pituitary gland. This study was designed to evaluate the effects of bisphenol-A (BPA) and octylphenol (OP) on steroidogenesis and feedback system in testicular cells of pre-pubertal mice. Mouse testicular cells were cultured in DMEM supplemented with human FSH (0.1 IU/ml), testosterone (10-7 M), and fetal bovine serum (10%) or medium with estrogen (E2), bisphenol-A and octylphenol (10-9, 10-7, and 10-5 M, respectively) for 48 hours. P450scc, 3 -HSD, P45017 and SF-1 mRNA were detected by RT-PCR. The expression of , A and B subunits of inhibin were also detected. After incubation of testicular cells for 48 hours in the presence of BPA or OP, the expression of CYPscc, 3 -HSD and CYP17 mRNA were significantly decreased but the expression of SF-1 were not changed except in positive control treated with E2. The expression of a subunit of inhibin was increased at the highest concentration of OP. There are no differences in the expression of A and B subunits of inhibin. Further studies are required to elucidate whether BPA and OP has an effect on feedback loop in male reproductive system. In conclusion, BPA and OP might inhibit steroidogenesis by decreasing the CYPscc, 3 -HSD and CYP17 mRNA expression in the mouse testis. These results suggest that BPA and OP would disturb testicular function and subsequently impair spermatogenesis. (This study was supported by grant R02-2001-00399 from KOSEF).
KEY WORDS: Environmetal estrogens, Spermatogenic cells, Steroidogenesis, Inhibin
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