A basic and clinical study on regulatory mechanism operating for the function of human corpus luteum

本研究的主要目的是阐明在生理条件下人体黄体功能即类固醇的产生受到调控的机制，从而为我们更好地理解黄体期缺陷这一重要但鲜为人知的不育原因提供生理学基础。通过体外和体内方法，我们能够揭示迄今为止未知的人类黄体调节机制的重要方面。首先，我们发现人类黄体由两种细胞组成，即L细胞和S细胞，它们的功能分别类似于卵巢卵泡的颗粒细胞和鞘细胞。L细胞在黄体酮的产生和芳香化酶活性方面是S细胞的两倍，而在雄激素的产生方面则相反。对hCG的反应性，表现为雄激素和黄体酮的增强，只发生在S细胞中。然而，更多的L细胞和S细胞能够芳香化雄激素，而在雄激素底物存在的情况下，fsh诱导的雌激素产生的刺激仅在L细胞中被激发。因此，我们认为在两种不同的促性腺激素的控制下，人类黄体两种黄体细胞之间的合作相互作用是有效的。其次，利用从中型卵泡中获得的猪颗粒细胞，我们首次证明了基础和lh刺激的黄体酮的产生受到白细胞介素-1的抑制。在LH存在下，这些细胞的形态黄体化也被这种淋巴因子所抑制。在体内研究中，我们已经表明，在黄体期正常女性体内注射FSH可提高循环雌二醇水平，从而为FSH可能参与黄体功能调节提供了证据。这些来自体内研究的结果与上述体外研究的结果一致。综上所述，本项目的研究结果对理解人类黄体功能的调控机制具有重要意义。少

The primary object of this study was to elucidate the mechanism through which the function of human corpora lutea, namely the production of steroids, is regulated under the physiologic condition, thereby providing a physiologic basis for our better understanding of luteal phase defect, an important but poorly understood cause of infertility. Using both in vitro and in vivo methods, we were able to disclose hitherto unknown important aspects of the regulatory mechanism of human corpora lutea. Firstly, we have shown that human corpora lutea are consisted of two types of cells, namely L and S cells, which are functionally analogous to granulosa and thecal cells of ovarian follicles, respectively. L cells are twice as potent in the production of progesterone and in the aromatase activity as S cells, whereas the reverse is true as regards the production of androgens. Reactivity to hCG, as manifested by an enhanced production of androgens and progesterone, occurs only in S cells. Whereas bot … More h L and S cells are capable of aromatizing androgens, FSH-induced stimulation of estrogen production under the presence of androgen substrate was elicited only in L cells. It is therefore proposed that co-oparative interraction between the two types of luteal cells of human copora lutea is operative under the control of two different gonadoropins. Secondly, using porcine granulosa cells obtained from medium-sized follicles, we have for the first time shown that basal as well as LH-stimulated production of progesterone is inhibited by interleukin-1. Morphological lutenization of these cells under th presence of LH was also inhibited by this lymphokine. In in vivo studies, we have shown that circulating levels of estradiol are elevated by the administration of FSH into nomal women in their luteal phase, thereby providing evidence for the possible participation of FSH in the regulation of corpus luteal function. These results from in vivo studies consort with those from in vitro studies described above. In summary, the results from this project do contribute significantly to the understanding of the regulatory mechanism of human corpora lutea function. Less