Inhibition of hCG-stimulated steroidogenesis in cultured mouse Leydig tumor cells by bisphenol A and octylphenols

Some environmental chemicals exhibit estrogenic or antiandrogenic activity. Some of these, such as bisphenol A (bis A) and octylphenols, are used in l arge amounts in many applications. We have analyzed the effects of bis A an d octylphenols on steroidogenesis in Leydig cells by measuring the LH recep tor-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 concentrati on, the hCG-stimulated cAMP and P formation in these cells was inhibited. B is 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 diethylstilbe sterol (DES) at the concentration of 10(-8) mol/liter had no inhibitory eff ect on cAMP formation stimulated by hCG or Fk but P production was inhibite d. Similarly, both estrogens inhibited P production stimulated by 8-Br-cAMP . Bis A or octylphenols had no effect on I-125-hCG binding to Leydig cell L H-receptors. Thus, these environmental chemicals appear to inhibit cAMP for mation and steroidogenesis in mLTC-1 Leydig tumor cells by preventing the c oupling between LH receptor and the adenylate cyclase. Since, estradiol did not inhibit hCG-stimulated cAMP production, the effects of bis A and octyl phenols may not be estrogen related. This emphasizes the complexity of endo crine disruption: chemicals show multiple endocrine activities that may dis turb several organs in distinct ways, (C) 1999 Academic Press.