title: Inhibition of hCG-stimulated steroidogenesis in cultured mouse Leydig tumor cells by bisphenol A and octylphenols.
abstract: Some environmental chemicals exhibit estrogenic or antiandrogenic activity. Some of these, such as bisphenol A (bis A) and octylphenols, are used in large amounts in many applications. We have analyzed the effects of bis A and octylphenols on steroidogenesis in Leydig cells by measuring the LH receptor-mediated cAMP and progesterone (P) production in cultured mouse Leydig tumor cells (mLTC-1 cells). After preincubation of mLTC-1 cells for 48 h in the presence of bis A or one of the octylphenols in micromolar concentration, the hCG-stimulated cAMP and P formation in these cells was inhibited. Bis A or octylphenols could neither inhibit cAMP nor P formation stimulated by forskolin (Fk) or cholera toxin (CT) nor steroidogenesis stimulated by 8-Br-cAMP. The preincubation of mLTC-1 cells with estradiol or diethylstilbesterol (DES) at the concentration of 10(-8) mol/liter had no inhibitory effect on cAMP formation stimulated by hCG or Fk but P production was inhibited. Similarly, both estrogens inhibited P production stimulated by 8-Br-cAMP. Bis A or octylphenols had no effect on 125I-hCG binding to Leydig cell LH-receptors. Thus, these environmental chemicals appear to inhibit cAMP formation and steroidogenesis in mLTC-1 Leydig tumor cells by preventing the coupling between LH receptor and the adenylate cyclase. Since, estradiol did not inhibit hCG-stimulated cAMP production, the effects of bis A and octylphenols may not be estrogen related. This emphasizes the complexity of endocrine disruption: chemicals show multiple endocrine activities that may disturb several organs in distinct ways.
authors.affiliation: Department of Physiology, University of Turku, Turku, FIN-20520, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Nikula
authors.forename: T
authors.initials: T
authors.lastname: Talonpoika
authors.forename: M
authors.initials: M
authors.lastname: Kaleva
authors.forename: J
authors.initials: J
authors.lastname: Toppari
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001559:Benzhydryl Compounds; D002772:Cholera Toxin / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004785:Environmental Pollutants / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D007984:Leydig Cell Tumor; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D011374:Progesterone / Q000096:biosynthesis; D011974:Receptors, LH / Q000378:metabolism; D013256:Steroids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D000098826:Bisphenol A Compounds
chemical_list: D015124:8-Bromo Cyclic Adenosine Monophosphate; D001559:Benzhydryl Compounds; D002772:Cholera Toxin; D006063:Chorionic Gonadotropin; D005576:Colforsin; D000242:Cyclic AMP; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D011374:Progesterone; D011974:Receptors, LH; D013256:Steroids; C080417:4-octylphenol; C105260:4-tert-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds