title: In vitro effects of diethylstilbestrol, genistein, 4-tert-butylphenol, and 4-tert-octylphenol on steroidogenic activity of isolated immature rat ovarian follicles.
abstract: Isolated rat ovarian follicles grow and produce steroid hormones in vitro and so provide a good model for studying the effects of hormonally active compounds on follicular steroidogenesis. We have evaluated the effects of diethylstilbestrol (DES), genistein (GEN) and two alkylphenols, 4-tert-butylphenol (BP) and 4-tert-octylphenol (OP) on the growth, survival, and steroid hormone and cAMP production by isolated 14-day-old rat (Sprague-Dawley) ovarian follicles. During a 5-day culture, FSH was obligatory for follicle growth and increased estradiol and testosterone secretion in a dose-dependent manner. DES (10(-6) M) caused the strongest decline in estradiol and testosterone levels but did not have detectable effects on either cAMP production or aromatase enzyme activity. GEN caused a prominent decrease in cAMP and testosterone levels without significant changes in secreted estradiol. The latter, apparently, was due to a dose-dependent stimulation of aromatase enzyme activity in the presence of genistein. Both BP and OP decreased estradiol and testosterone secretion in a dose-dependent manner while no effect on aromatase activity was observed. OP, unlike BP, decreased forskolin-induced cAMP levels. Xenoestrogens at the used concentrations did not interfere with the growth and survival of the follicles. The results indicate that isolated ovarian follicles representing intact morphological and functional units offer a sensitive model system for elucidating the female-specific reproductive effects of environmental chemicals.
authors.affiliation: Department of Biology, Laboratory of Animal Physiology, 20014 University of Turku, Turku, Finland. saanmy@utu.fi
authors.forename: Sari
authors.initials: S
authors.lastname: Myllymäki
authors.forename: Tapio
authors.initials: T
authors.lastname: Haavisto
authors.forename: Minna
authors.initials: M
authors.lastname: Vainio
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.forename: Jorma
authors.initials: J
authors.lastname: Paranko
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004054:Diethylstilbestrol / Q000633:toxicity*; D004958:Estradiol / Q000096:biosynthesis; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D019833:Genistein / Q000633:toxicity*; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010636:Phenols / Q000633:toxicity*; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000096:biosynthesis; D018675:Toxicity Tests
chemical_list: D004967:Estrogens; D010636:Phenols; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone; D019833:Genistein; D000242:Cyclic AMP; D001141:Aromatase; C105260:4-tert-octylphenol; C006862:butylphen