Calogero A E, Burrello N, Ossino A M, Polosa P, D'Agata R
Department of Internal Medicine, University of Catania, Italy.
J Endocrinol. 1998 Feb;156(2):269-74. doi: 10.1677/joe.0.1560269.
The presence of activins in those hypothalamic regions containing gonadotropin-releasing hormone (GnRH)-secreting neurons suggests that these peptides may regulate the reproductive function modulating not only pituitary FSH release and biosynthesis, but also hypothalamic GnRH release. The purpose of this study was to evaluate the effects of activin-A, a homodimer of inhibin beta A subunit, on hypothalamic GnRH release in vitro and, because of their well known antithetical effects, to evaluate its interaction with inhibin. In addition, since androgens modulate the release of GnRH from male rat hypothalami, we thought it of interest to study the possible interplay between these steroids and activin on GnRH release. To accomplish this, we employed a hypothalamic organ culture system which enabled us to evaluate GnRH release from individually incubated hemi-hypothalami explanted from male rats. Activin-A stimulated GnRH release in a biphasic manner. The maximal effect was reached at a concentration of 10 ng/ml which increased GnRH output by about 75%. Inhibin abolished the stimulatory effect of a maximally effective concentration of activin-A in a dose-dependent manner, whereas alone it had no effect on GnRH output. As previously shown, testosterone (1 nmol/l) and dihydrotestosterone (DHT, 0.1 nmol/l) suppressed basal GnRH release, but only testosterone was able to inhibit the release of GnRH stimulated by activin-A. Since DHT is a non-aromatizable androgen, we evaluated whether the inhibitory effect of testosterone was due to its in vitro conversion into 17 beta-estradiol. The addition of 4-hydroxyandrostenedione, a steroidal aromatase inhibitor, did not influence the suppressive effect of testosterone on GnRH release stimulated by activin-A. In conclusion, activin-A stimulated hypothalamic GnRH release in vitro and this effect was abolished by inhibin and was blunted by testosterone. These findings suggest that activins may participate in the regulation of the hypothalamic-pituitary-gonadal axis by modulating GnRH release. The ability of testosterone to suppress the release of GnRH stimulated by activin-A indicates that this steroid has a potent negative feedback influence on GnRH release.
在那些含有分泌促性腺激素释放激素（GnRH）的神经元的下丘脑区域中存在激活素，这表明这些肽可能通过调节垂体促卵泡激素（FSH）的释放和生物合成，以及下丘脑GnRH的释放来调节生殖功能。本研究的目的是评估抑制素βA亚基的同二聚体激活素-A对体外下丘脑GnRH释放的影响，并鉴于其众所周知的相反作用，评估其与抑制素的相互作用。此外，由于雄激素可调节雄性大鼠下丘脑GnRH的释放，我们认为研究这些类固醇与激活素在GnRH释放上可能的相互作用很有意义。为实现这一目标，我们采用了下丘脑器官培养系统，该系统使我们能够评估从雄性大鼠分离培养的单个半下丘脑植入物中GnRH的释放。激活素-A以双相方式刺激GnRH释放。在浓度为10 ng/ml时达到最大效应，此时GnRH输出增加约75%。抑制素以剂量依赖性方式消除了最大有效浓度的激活素-A的刺激作用，而单独使用时对GnRH输出没有影响。如先前所示，睾酮（1 nmol/l）和双氢睾酮（DHT，0.1 nmol/l）抑制基础GnRH释放，但只有睾酮能够抑制激活素-A刺激的GnRH释放。由于DHT是一种不可芳香化的雄激素，我们评估了睾酮的抑制作用是否由于其在体外转化为17β-雌二醇。添加甾体芳香化酶抑制剂4-羟基雄烯二酮并不影响睾酮对激活素-A刺激的GnRH释放的抑制作用。总之，激活素-A在体外刺激下丘脑GnRH释放，这种作用被抑制素消除，并被睾酮减弱。这些发现表明激活素可能通过调节GnRH释放参与下丘脑-垂体-性腺轴的调节。睾酮抑制激活素-A刺激的GnRH释放表明该类固醇对GnRH释放具有强大的负反馈影响。
