Turgeon J L, Waring D W
Department of Human Physiology, University of California School of Medicine, Davis 95616, USA.
Endocrinology. 1999 Apr;140(4):1767-74. doi: 10.1210/endo.140.4.6642.
In the female, androgens can have negative and positive actions in the regulation of LH, but it is not clear how they may function during the reproductive cycle. Toward resolving these potentially conflicting roles for androgen, we used an in vitro model of preovulatory gonadotropes to examine the effect of proestrous levels of testosterone (1.7 nM) or dihydrotestosterone (DHT; 0.7 nM) on LH secretion in response to pulsatile GnRH (1 nM) or elevated extracellular K+ (54 mM). For female rat pituitary cells cultured in 17beta-estradiol (E2)-containing medium, androgen treatment for 16 h, but not for 4 h, inhibited the LH secretory response to a pulse of either GnRH or K+ by about 60% and suppressed the acute augmentation action of 20 nM progesterone on GnRH- or K+-induced LH secretion. In the absence of E2, DHT also decreased LH secretion induced by a pulse of GnRH. DHT's suppressive effect on progesterone could be partially overcome with increased progesterone (200 nM) or by removal of DHT during progesterone exposure. For pituitary cells transfected with a reporter plasmid containing three progesterone response elements, DHT only partially suppressed progesterone-stimulated transcriptional activity. The positive action of androgen (16 h) on LH secretion was elicited by multiple GnRH pulses with a latency of about 2 h after the first pulse; this facilitatory action of androgen did not require an E2 background and, therefore, is distinct from GnRH self priming. In summary, these data demonstrate both facilitatory and inhibitory actions of androgen on LH secretion function in female gonadotropes in vitro in the absence or presence of E2; these actions occur with a time course suggestive of a role for androgen in shaping the preovulatory LH surge. Androgen also markedly suppresses progesterone augmentation of stimulated LH secretion, which could be due in part to interference with the trans-activation function of the progesterone receptor.
在女性中，雄激素在促黄体生成素（LH）的调节中可产生负性和正性作用，但它们在生殖周期中如何发挥作用尚不清楚。为了解决雄激素这些潜在的相互矛盾的作用，我们使用排卵前促性腺激素细胞的体外模型，研究动情前期水平的睾酮（1.7 nM）或双氢睾酮（DHT；0.7 nM）对促性腺激素释放激素（GnRH，1 nM）脉冲或细胞外钾离子浓度升高（54 mM）刺激下LH分泌的影响。对于培养在含17β-雌二醇（E2）培养基中的雌性大鼠垂体细胞，雄激素处理16小时而非4小时，可使对GnRH或钾离子脉冲的LH分泌反应抑制约60%，并抑制20 nM孕酮对GnRH或钾离子诱导的LH分泌的急性增强作用。在无E2时，DHT也可降低GnRH脉冲诱导的LH分泌。增加孕酮（200 nM）或在孕酮作用期间去除DHT可部分克服DHT对孕酮的抑制作用。对于转染了含三个孕酮反应元件的报告质粒的垂体细胞，DHT仅部分抑制孕酮刺激的转录活性。雄激素（16小时）对LH分泌的正性作用由多个GnRH脉冲引发，在第一个脉冲后约2小时出现延迟；雄激素的这种促进作用不需要E2背景，因此不同于GnRH自身启动。总之，这些数据表明，在有或无E2的情况下，雄激素在体外对雌性促性腺激素细胞的LH分泌功能具有促进和抑制作用；这些作用的发生时间进程提示雄激素在塑造排卵前LH峰中起作用。雄激素还显著抑制刺激后的LH分泌的孕酮增强作用，这可能部分归因于对孕酮受体反式激活功能的干扰。
