Involvement of the orphan nuclear receptor SF-1 in the effect of PCBs, DDT and DDE on the secretion of steroid hormones and oxytocin from bovine granulosa cells.
Polychlorinated biphenyls (PCBs), DDT and its metabolite (DDE) belong to estrogen-like endocrine disruptors. However, though their activity is approximately 1000-fold lower than the activity of estradiol (E2), this steroid's high concentration in follicular fluid and incubation media does not inhibit the influence of these xenobiotics. It was hypothesized that these xenobiotics might affect Steroidogenic Factor-1 (SF-1) and impair ovary function. To test this hypothesis, granulosa cells were obtained from ovarian follicles >1 or <1cm in diameter, which were treated with PCB-77, PCB-153, DDT or DDE (each at 10ng/ml), alone or jointly with an SF-1 antagonist (F0160). Treatment with the SF-1 antagonist inhibited (P<0.05) the secretion of P4 from cells of both sizes of follicles, as induced (P<0.05) by an SF-1 activator (HxP), DDE or PCB-153. All xenobiotics and HxP stimulated (P<0.05) the synthesis and secretion of oxytocin (OT). However, the effect on mRNA expression for NP-I/OT, which is OT precursor, was inhibited (P<0.05) by F0160 in all cultures treated with PCB-77, except for granulosa cells derived from follicles <1cm. Moreover, F0160 inhibited the effect on OT secretion of HxP, as well as all xenobiotics except for PCB-77 and DDE, in granulosa cells derived from follicles <1cm. Xenobiotic treatment did not affect (P>0.05) the expression for SF-1 mRNA. It is suggested that the SF-1 receptor may be involved in the adverse effects of xenobiotics on P4 secretion as well as the synthesis and secretion of OT.
Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Tuwima St 10, 10-747 Olsztyn, Poland.
J
J
Mlynarczuk
M H
MH
Wrobel
A
A
Ziolkowska
J
J
Kotwica
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003634:DDT / Q000494:pharmacology*; D003633:Dichlorodiphenyl Dichloroethylene / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D057093:Orphan Nuclear Receptors / Q000502:physiology; D010121:Oxytocin / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D054339:Steroidogenic Factor 1 / Q000037:antagonists & inhibitors / Q000502:physiology*
D004146:Dioxanes; D012739:Gonadal Steroid Hormones; D007546:Isoquinolines; D057093:Orphan Nuclear Receptors; D054339:Steroidogenic Factor 1; C000591236:ethyl 2-(2-(2-(2,3-dihydro-1,4-benzodioxin-7-ylamino)-2-oxoethyl)-1-oxoisoquinolin-5-yl)oxypropanoate; D003633:Dichlorodiphenyl Dichloroethylene; D010121:Oxytocin; D003634:DDT; D011078:Polychlorinated Biphenyls
DDT; Granulosa; Oxytocin; PCBs; SF-1; Steroidogenesis