Rehnberg G L, Linder R E, Goldman J M, Hein J F, McElroy W K, Cooper R L
Endocrinology/Gerontology Section, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Toxicol Appl Pharmacol. 1988 Sep 15;95(2):255-64. doi: 10.1016/0041-008x(88)90162-7.
m-Dinitrobenzene (m-DNB)-induced testicular atrophy has been attributed to a direct effect upon the germinal epithelium. However, such degenerative changes in the germinal epithelium should induce shifts in the testicular hormonal milieu, which would in turn alter the hypothalamic-pituitary gonadal axis in general. This study evaluated the endocrine status of male rats (killed 3 hr, 24 hr, 1 week, and 2 weeks) following a single oral dose of m-DNB (32 mg m-DNB/kg). Serum and pituitary leuteinizing hormone, follicle-stimulating hormone (FSH), and protactin and hypothalamic gonadotropin-releasing hormone (GnRH) concentrations were determined. Testosterone and androgen-binding protein concentrations in serum, interstitial fluid, seminiferous tubule fluid, and caput epididymis were also determined. In vitro basal and hCG-stimulated testosterone release was determined in the decapsulated testis. Results of the present study indicate that pituitary hormone concentrations and hypothalamic GnRH were unaffected after a single oral dose of m-DNB. Serum FSH was elevated at 2 weeks. There was a transient decrease in serum testosterone at 24 hr, which returned to control values at 1 and 2 weeks. Interstitial fluid, seminiferous tubule fluid, and caput epididymal testosterone concentrations were increased at 1 and 2 weeks. Basal testosterone release in vitro was increased at 2 weeks, while hCG-stimulated testosterone release was increased at 1 and 2 weeks. Androgen-binding protein concentrations in serum and interstitial fluid were increased at 1 and 2 weeks. Androgen-binding protein was increased at 24 hr and 1 week in seminiferous tubule fluid, but returned to control concentrations by 2 weeks. However, the total tubular content of androgen-binding protein was dramatically decreased at 2 weeks. Androgen-binding protein in the caput epididymis was unaltered following m-DNB treatment. These data demonstrate that m-DNB exerts a direct effect on the testes and not through alterations in hypothalamic and pituitary control of gonadal function.
间二硝基苯（m-DNB）诱导的睾丸萎缩被认为是对生精上皮的直接作用所致。然而，生精上皮的这种退行性变化应会引起睾丸激素环境的改变，进而总体上改变下丘脑-垂体-性腺轴。本研究评估了单次口服m-DNB（32毫克m-DNB/千克）后雄性大鼠（在3小时、24小时、1周和2周时处死）的内分泌状态。测定了血清和垂体中的促黄体生成素、促卵泡激素（FSH）、泌乳素以及下丘脑促性腺激素释放激素（GnRH）的浓度。还测定了血清、间质液、生精小管液和附睾头中的睾酮及雄激素结合蛋白浓度。在去包膜睾丸中测定了体外基础及人绒毛膜促性腺激素（hCG）刺激后的睾酮释放。本研究结果表明，单次口服m-DNB后垂体激素浓度和下丘脑GnRH未受影响。血清FSH在2周时升高。血清睾酮在24小时时有短暂下降，在1周和2周时恢复至对照值。间质液、生精小管液和附睾头的睾酮浓度在1周和2周时升高。体外基础睾酮释放在2周时增加，而hCG刺激后的睾酮释放在1周和2周时增加。血清和间质液中的雄激素结合蛋白浓度在1周和2周时升高。生精小管液中的雄激素结合蛋白在24小时和1周时增加，但到2周时恢复至对照浓度。然而，雄激素结合蛋白的总小管含量在2周时显著降低。m-DNB处理后附睾头中的雄激素结合蛋白未改变。这些数据表明，m-DNB对睾丸有直接作用，而非通过改变下丘脑和垂体对性腺功能的控制来起作用。
