摘要：19 名男性受试者每天注射17β-雌二醇，共5次，并在类固醇疗程之前、期间和之后通过放射免疫测定法测定雌二醇 (E2)、睾酮 (T) 和促性腺激素的循环水平。在 5 天的治疗期间达到的 E2 峰值水平为 173-577 pg/ml。七名正常成年男性中有四名和一名去势男性表现出促卵泡激素 (FSH) 和促黄体生成素 (LH)的抑制，随后 LH 升高（正反馈），而 E2 水平保持升高。 T 的升高与四名正常男性的 LH 增加有关。九名青春期前、早期或中期男孩和两名患有低促性腺激素性腺功能减退症的男性在 E2 给药后仅显示促性腺激素抑制。与内分泌正常的男孩相比，促性腺激素水平正常或升高的成年男性对雌激素的 LH 反应（即正反馈）差异显着（P < 0.01）。
推测：雌激素和 LH 之间的正反馈存在于完整的成年男性中，尽管这种反应的幅度和一致性低于女性。男性的睾酮在雌性恒河猴中的作用可能类似于孕酮，以减弱雌激素给药期间 LH 升高的幅度。正反馈的能力似乎是在男性和女性青春期发生的成熟事件。
The LH surge in humans: its mechanism and sex difference
There is a sex difference in the response to an estrogen challenge test in humans, but, unlike with rats, this sex difference is not permanently imprinted in the central nervous system. Estrogen is not only the important ovarian signal to trigger off the LH surge, but it also probably plays an important role in activating the positive estrogen feedback mechanism in humans. For an LH surge to occur, amplification of the hypothalamic signal (enhanced secretion of GnRH) as well as sensitization of the pituitary responsiveness to GnRH are required. It is unlikely that androgens per se are responsible for suppressing the positive estrogen feedback in humans and the possible role of another gonadal factor other than androgens remains speculative. The LH surge is a neuroendocrine phenomenon involved primarily in the process of ovulation and it is not correlated to sexual identity and orientation. Furthermore, how the hypothalamic-pituitary axis (HPA) responds to the estrogen challenge can be accounted for purely by its exposure to a different steroid milieu without reference to gender identity or sexual orientation of the subject.
Neuroendocrine mechanisms underlying estrogen positive feedback and the LH surge
A fundamental principle in reproductive neuroendocrinology is sex steroid feedback: steroid hormones secreted by the gonads circulate back to the brain to regulate the neural circuits governing the reproductive neuroendocrine axis. These regulatory feedback loops ultimately act to modulate gonadotropin-releasing hormone (GnRH) secretion, thereby affecting gonadotropin secretion from the anterior pituitary. In females, rising estradiol (E2) during the middle of the menstrual (or estrous) cycle paradoxically “switch” from being inhibitory on GnRH secretion (“negative feedback”) to stimulating GnRH release (“positive feedback”), resulting in a surge in GnRH secretion and a downstream LH surge that triggers ovulation. While upstream neural afferents of GnRH neurons, including kisspeptin neurons in the rostral hypothalamus, are proposed as critical loci of E2 feedback action, the underlying mechanisms governing the shift between E2 negative and positive feedback are still poorly understood. Indeed, the precise cell targets, neural signaling factors and receptors, hormonal pathways, and molecular mechanisms by which ovarian-derived E2 indirectly stimulates GnRH surge secretion remain incompletely known. In many species, there is also a circadian component to the LH surge, restricting its occurrence to specific times of day, but how the circadian clock interacts with endocrine signals to ultimately time LH surge generation also remains a major gap in knowledge. Here, we focus on classic and recent data from rodent models and discuss the consensus knowledge of the neural players, including kisspeptin, the suprachiasmatic nucleus, and glia, as well as endocrine players, including estradiol and progesterone, in the complex regulation and generation of E2-induced LH surges in females.