Culler M D
Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Endocrinology. 1990 Nov;127(5):2540-50. doi: 10.1210/endo-127-5-2540.
The purpose of the present study was to determine the parameters of pulsatile gonadotropin secretion in the adult male rat that are regulated by the suppressive feedback influences provided by factors originating in the Leydig cells or by endogenous inhibin, or both. This was achieved by examining the changes in the secretion parameters of FSH and LH that result from selectively destroying the Leydig cells using the toxicant ethane dimethane sulfonate (EDS) or passively immunoneutralizing endogenous inhibin using high-titer anti alpha-inhibin subunit serum, or both. Both FSH and LH were secreted in a pulsatile manner in intact male rats as determined using two different pulse-detection methods. Destruction of the Leydig cells with EDS 6 days before sampling significantly increased basal FSH secretion without affecting pulsatile FSH secretion. Injection of anti-inhibin serum into intact (vehicle treated) males 18 h before sampling produced no observable alteration in any parameter of FSH secretion. Either administration of anti-inhibin serum or castration of rats previously treated with EDS induced further significant, selective increases in the basal parameters of FSH secretion, raising mean FSH to levels comparable to those observed in 6-day castrate rats. When examined individually, however, the parameters of mean trough and peak FSH level and mean pulse amplitude remained significantly higher in the 6-day castrate males. In sharp contrast to the selective effects on basal FSH, destruction of the Leydig cells with EDS dramatically elevated all parameters of LH secretion to levels comparable to those observed in similarly timed castrate rats. Neither immunoneutralization of endogenous inhibin nor castration of EDS-treated rats 18 h before sampling caused any further alteration in any parameter of LH secretion. The results from these studies demonstrate that the Leydig cell provides all of the suppressive influence of the testes on LH secretion and a major portion of the suppressive influence over FSH secretion. This influence is exerted through a suppression of all parameters of LH secretion, but through a selective suppression of basal FSH secretion parameters. Collectively, the results suggest that the Leydig cell-derived influences suppress those parameters of gonadotropin secretion that are mediated by LHRH, acting, at least in part, through a suppression of pituitary sensitivity to LHRH. In the absence of the Leydig cells, endogenous inhibin can be demonstrated to also suppress basal FSH secretion in the adult male rat.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究的目的是确定成年雄性大鼠中脉冲式促性腺激素分泌的参数，这些参数受睾丸间质细胞来源的因子或内源性抑制素或两者提供的抑制性反馈影响的调节。这是通过检查使用有毒物质乙烷二甲磺酸盐（EDS）选择性破坏睾丸间质细胞，或使用高滴度抗α-抑制素亚基血清被动免疫中和内源性抑制素，或两者兼而有之，所导致的促卵泡激素（FSH）和促黄体生成素（LH）分泌参数的变化来实现的。使用两种不同的脉冲检测方法确定，完整雄性大鼠中的FSH和LH均以脉冲方式分泌。在采样前6天用EDS破坏睾丸间质细胞显著增加了基础FSH分泌，而不影响FSH的脉冲式分泌。在采样前18小时向完整（接受载体处理）的雄性大鼠注射抗抑制素血清，未观察到FSH分泌的任何参数有明显改变。给予抗抑制素血清或对先前用EDS处理的大鼠进行阉割，均可进一步显著、选择性地增加FSH分泌的基础参数，使平均FSH水平升高至与6天去势大鼠中观察到的水平相当。然而，单独检查时，6天去势雄性大鼠的平均谷值和峰值FSH水平以及平均脉冲幅度参数仍显著更高。与对基础FSH的选择性作用形成鲜明对比的是，用EDS破坏睾丸间质细胞会使LH分泌的所有参数急剧升高至与同期去势大鼠中观察到的水平相当。在采样前18小时，对用EDS处理的大鼠进行内源性抑制素的免疫中和或阉割，均未导致LH分泌的任何参数有进一步改变。这些研究结果表明，睾丸间质细胞提供了睾丸对LH分泌的所有抑制性影响以及对FSH分泌的大部分抑制性影响。这种影响是通过抑制LH分泌的所有参数来施加的，但通过选择性抑制基础FSH分泌参数来实现。总体而言，结果表明睾丸间质细胞衍生的影响抑制了由促性腺激素释放激素（LHRH）介导的促性腺激素分泌参数，至少部分是通过抑制垂体对LHRH的敏感性来实现的。在没有睾丸间质细胞的情况下，可以证明内源性抑制素也能抑制成年雄性大鼠的基础FSH分泌。（摘要截于400字）
