Differing effects of endocrine-disrupting chemicals on basal and FSH-stimulated progesterone production in rat granulosa-luteal cells.
Previous studies have shown that the phytoestrogen, genistein, inhibits basal and forskolin-stimulated progesterone synthesis in rat granulosa-luteal cells. Genistein, however, not only binds and activates the estrogen receptor (ER), but is also a potent inhibitor of tyrosine kinase. In these studies we have compared the effects of estradiol, two other phytoestrogens, apigenin and coumarin, the pesticide, [2-(chlorphenyl)-2-(4-chlorphenyl)-1,1,1-trichlorethan] (2,4'DDT), and the industrial chemical, 4-octyl-phenol, on basal and follicle stimulating hormone (FSH)-stimulated progesterone production in the same experimental system. Only a supraphysiological dose of estradiol (10(-5) M) significantly inhibited basal and forskolin-stimulated progesterone production in granulosa-luteal cells, but had no effect on FSH-stimulated production. In contrast, apigenin, DDT, and octyl-phenol stimulated basal progesterone production at doses around 10(-8) to 10(-7) M, but this effect was reversed at higher doses. Coumarin was without effect. Like basal production, the two phytoestrogens had opposing effects on FSH-stimulated progesterone production. Genistein at 10(-5) M was inhibitory, while apigenin significantly potentiated the response at 19(-7) M. In contrast, DDT had no effect on the FSH-induced response, though 10(-7) M octyl-phenol nearly doubled the response. While all these chemicals are known to interact with the estrogen receptor to a greater or lesser extent, these studies suggest that like genistein, these different endocrine-disrupting chemicals may have other actions apart from those on the estrogen receptor.
Nejaty
H
H
Department of Physiology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom.
Lacey
M
M
Whitehead
S A
SA
D000818:Animals; D047310:Apigenin; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology; D003634:DDT / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D003374:Coumarins; D004967:Estrogens; D005419:Flavonoids; D010636:Phenols; D005576:Colforsin; D011374:Progesterone; D004958:Estradiol; C080417:4-octylphenol; D047310:Apigenin; D005640:Follicle Stimulating Hormone; C030123:coumarin; D003634:DDT; C016340:o,p'-DDT; D019833:Genistein