Differential effects of octylphenol, 17 beta-estradiol, endosulfan, or bisphenol A on the steroidogenic competence of cultured adult rat Leydig cells

In the current studies, we evaluated the effects of 4-tert-octylphenot (OP) , endosulfan, bisphenol A (BPA), and 17 beta -estradiol on basal or hCG-sti mulated testosterone formation by cultured Leydig cells from young adult ma le rats. Exposure of Leydig cells to increasing concentrations of OP (1 to 2000 nM), 17 beta -estradiol (1 to 1000 nM). endosulfan (1 to 1000 nM) or B PA (1 to 1000 nM), alone or with 10 mIU/mL hCG for 4 or 24 h, did not lower ambient testosterone levels, although cells exposed to higher OP concentra tions + hCG for 24 h often had modest declines in testosterone (10 to 20%). Of interest, exposure to the highest concentration OP (2000 nM) alone for 4 or 24 h increased testosterone levels (similar to 2-fold in 4-h exposed c ells). Whether prior exposure to OP + hCG for 24 It affects the subsequent conversion of steroid substrates to testosterone over 4 It was evaluated. P rogressive declines in 1 muM 22(R) hydroxycholesterol, 1 muM pregnenolone, or 1 muM progesterone conversion to testosterone was observed beginning at 100 to 500 nM OP exposure (maximal declines of 40 to 12% of controls were o bserved); however, the conversion of 1 muM androstenedione to testosterone was not affected by OP. These results suggested that 24-h exposure to OP hCG has no effect on 17 beta -hydroxysteroid dehydrogenase, which converts androstenedione to testosterone, but that it inhibits the 17 alpha -hydroxy lase/C17-20 lyase step, which converts progesterone to androstenedione. In addition, potentially, OP could inhibit cholesterol side/chain cleavage act ivity, which converts cholesterol to pregnenolone, and/or 3 beta -hydroxyst eroid dehydrogenase, which converts pregnenolone to progesterone. Of intere st, exposure to increasing concentrations of 17 beta -estradiol (1 to 1000 nM), endosulfan (1 to 1000 nM), or BPA (1 to 1000 nM) + hCG for 24 h had no effect on subsequent conversion of 22(R)hydroxycholesterol to testosterone . Furthermore, the inhibiting effects of OP + hCG exposure on subsequent co nversion of progesterone to testosterone was unaffected by concomitant expo sure to the pure estrogen antagonist, ICI 182,780, or the antioxidants, asc orbate or dimethyl sulfoxide, suggesting that the actions of OP are not med iated through binding to estrogen receptor alpha or beta or by free radical induced damage to steroidogenic enzymes, respectively. These results demon strate that direct exposure of adult Leydig cells to OP may have subtle eff ects on their ability to produce testosterone, which may not be detected by measuring ambient androgen levels. In addition, the effects of OP on Leydi g cell testosterone formation appear to be different from those of the nati ve estrogen, 17 beta -estradiol, and from other reported weak xenoestrogens such as endosulfan and BPA. (C) 2001 Elsevier Science Inc. All rights rese rved.