Octylphenol (OP), a surfactant additive widely used in the manufacture of various detergents and other commercial products, bas been reported to mimic the actions of estrogen in many cellular systems. In the present studies, the direct effects of OP on basal and human chorionic gonadotropin (hCG)-stimulated testosterone production by cultured Leydig cells from neonata1 rats (6-7 days of age) were evaluated. Exposure of cultured cells to increasing concentrations of OP (1-2000 nM) and 10 mIU/mt bCG for 24 h caused a consistent biphasic pattern of testosterone response. Lower concentrations of OP enhanced testosterone levels (about 10- 70% above control), while higher OP concentrations (100-2000 nM) progressively decreased testosterone from peak levels to approximately 40-80% below control at the highest OP concentration. Interestingly, increasing concentrations of 17beta-estradiol (1-1000 nM) were without effect on testosterone formation under the same conditions, and the biphasic pattern of testosterone biosynthesis elicited by increasing concentrations of OP and hCG was unaffected by concommitant treatment with 10 or 100 nM ICI 182,780, which is considered a pure estrogen antagonist. Therefore, these actions of OP do not appear, to be mediated through the classic estrogen receptor alpha nor beta pathway. Because the biphasic pattern of testosterone biosynthesis was observed in response to exposure with increasing concentrations of OP and 0.1 mM 8-Br-cAMP, it appears that the main site(s) of action occurs following the generation of cAMP. In addition, because pretreatment of cells with increasing OP concentrations and hCG had no effect on the conversion of steroid precursors (1 microM each of 22 (R)-hydroxycholesterol, progesterone or androstenedione) to testosterone, it appears that the main actions of OP occur prior to the mitochondrial cholesterol side-chain cleavage step. Furthermore, because concommitant treatment of cells with antioxidants (alpha-tocopherol or butylated hydroxyanisole) did not alter the biphasic testosterone response pattern to increasing OP concentrations and hCG, it appears that OP is not acting as a pro-oxidant in producing these effects. It will be important to determine whether this dose-sensitive response to OP is observed in vivo and whether the maturational status of Leydig cells influences their sensitivity to OP and similar chemicals.
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana