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Inhibition of hCG-stimulated steroidogenesis in cultured mouse Leydig tumor cells by bisphenol A and octylphenols
Tekijät: Nikula H, Talonpoika T, Kaleva M, Toppari J
Julkaisuvuosi: 1999
Journal: Toxicology and Applied Pharmacology
Tietokannassa oleva lehden nimi: Toxicology and applied pharmacology
Lehden akronyymi: Toxicol Appl Pharmacol
Vuosikerta: 157
Numero: 3
Aloitussivu: 166
Lopetussivu: 73
Sivujen määrä: 8
ISSN: 0041-008X
DOI: https://doi.org/10.1006/taap.1999.8674
Tiivistelmä
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.
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.
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