TESTICULAR HORMONES & GONADOTROPINS IN MALE INFERTILITY

据估计，15%的夫妇将在某些地方寻求医疗服务 不孕不育的时间，男性因素将在50%的 这些案子。尽管大多数人类男性不育的病理生理学是 不确定，细菌受损男性最常见的内分泌异常 细胞发育是血清FSH水平的上升。的长期目标是 这些研究是为了了解不孕症患者的内分泌紊乱。 男人。本提案的目标1是研究 男性不育患者血清FSH和抑制素性质的检测 精索静脉曲张相关性不育症患者的睾丸分泌。 男性精索静脉血中抑制素的生化特征 随着FSH水平的正常和升高，将进行检查 假设各种免疫反应形式的抑制素与变量 生物活性是由人类的睾丸释放的。第二，大部分是什么 已知的细胞和分子机制的抑制素和 其他睾丸激素调节FSH的研究是在大鼠身上进行的。还没有 大鼠和大鼠垂体-睾丸功能的本质差异 人类已经被识别，所以概念是从对老鼠的研究中发展出来的 可能不适用于人类男性不育。因此，目标2是 用培养的非人垂体细胞建立模型系统 雄性灵长类动物为了更好地了解不育患者的FSH分泌 男人。促性腺激素分泌和亚单位信使RNA将在 单层培养的垂体细胞和灌流脉冲的细胞 GnRH。抑制素、激活素、卵泡抑素、睾酮、 将对这些细胞上的双氢睾酮和雌二醇进行检测。

It has been estimated that 15% of couples will seek medical care at some time for infertility, and that a male factor will be important in 50% of the cases. Although the pathophysiology of most human male infertility is uncertain, the most common endocrine abnormality in men with impaired germ cell development is a rise in serum FSH levels. The long term goal of these studies is to understand this endocrine disturbance in infertile men. Aim 1 of the present proposal is to study the relationship between serum FSH and inhibin in infertile men by examining the nature of inhibin secreted by the testis in men with varicocele-associated infertility. Biochemical characterization of inhibin in spermatic vein blood 'in men with normal and increased levels of FSH will be performed to examine the hypothesis that various immunoreactive forms of inhibin with variable bioactivity are released by the human testis. Second, most of what is known about the cellular and molecular mechanisms by which inhibin and other testicular hormones regulate FSH is from studies in rats. Yet substantial differences in pituitary-testicular function in the rat and man have been identified, so that concepts developed from studies in rats may not be applicable to human male infertility. Accordingly, Aim 2 is to establish a model system using cultured pituitary cells from the nonhuman male primate in an effort to better understand FSH secretion in infertile men. Gonadotropin secretion and subunit messenger RNAs will be studied in pituitary cells in monolayer culture and in cells perfused with pulses of GnRH. The actions of inhibin, activin, follistatin, testosterone, dihydrotestosterone and estradiol on these cells will be examined.