Department of Pediatrics, Johns Hopkins University School of Medicine Baltimore, MD, USA.
Front Endocrinol (Lausanne). 2012 Apr 9;3:52. doi: 10.3389/fendo.2012.00052. eCollection 2012.
Reproductive function is regulated by the secretion of luteinizing hormone (LH) and follicle-stimulating hormone from the pituitary and the steroid hormones from the gonads. The dynamic changes in the levels of the reproductive hormones regulate secondary sex characteristics, gametogenesis, cellular function, and behavior. Hypothalamic GnRH neurons, with cell bodies located in the basal hypothalamus, represent the final common pathway for neuronally derived signals to the pituitary. As such, they serve as integrators of a dizzying array of signals including sensory inputs mediating information about circadian, seasonal, behavioral, pheromonal, and emotional cues. Additionally, information about peripheral physiological function may also be included in the integrative signal to the GnRH neuron. These signals may communicate information about metabolic status, disease, or infection. Gonadal steroid hormones arguably exert the most important effects on GnRH neuronal function. In both males and females, the gonadal steroid hormones exert negative feedback regulation on axis activity at both the level of the pituitary and the hypothalamus. These negative feedback loops regulate homeostasis of steroid hormone levels. In females, a cyclic reversal of estrogen feedback produces a positive feedback loop at both the hypothalamic and pituitary levels. Central positive feedback results in a dramatic increase in GnRH secretion (Moenter et al., 1992; Xia et al., 1992; Clarke, 1993; Sisk et al., 2001). This is coupled with an increase in pituitary sensitivity to GnRH (Savoy-Moore et al., 1980; Turzillo et al., 1995), which produces the massive surge in secretion of LH that triggers ovulation. While feedback regulation of the axis in males is in part mediated by estrogen receptors (ER), there is not a clear consensus as to the relative role of ER versus AR signaling in males (Lindzey et al., 1998; Wersinger et al., 1999). Therefore, this review will focus on estrogenic signaling in the female.
生殖功能受垂体分泌的黄体生成素 (LH) 和卵泡刺激素以及性腺分泌的甾体激素的调节。生殖激素水平的动态变化调节着第二性征、配子发生、细胞功能和行为。下丘脑 GnRH 神经元的细胞体位于下丘脑底部，代表了神经元信号传递到垂体的最终共同途径。因此，它们是包括昼夜节律、季节性、行为、信息素和情绪线索等感觉输入介导的信息在内的各种信号的整合者。此外，关于外周生理功能的信息也可能包含在 GnRH 神经元的整合信号中。这些信号可能传达有关代谢状态、疾病或感染的信息。性腺甾体激素对 GnRH 神经元功能的影响可能最大。在男性和女性中，性腺甾体激素对垂体和下丘脑水平的轴活动都产生负反馈调节。这些负反馈环调节甾体激素水平的内稳态。在女性中，雌激素反馈的周期性逆转在下丘脑和垂体水平产生正反馈环。中枢正反馈导致 GnRH 分泌的急剧增加（Moenter 等人，1992 年；Xia 等人，1992 年；Clarke，1993 年；Sisk 等人，2001 年）。这伴随着垂体对 GnRH 的敏感性增加（Savoy-Moore 等人，1980 年；Turzillo 等人，1995 年），这导致了 LH 的大量激增，从而引发排卵。虽然男性轴的反馈调节部分受雌激素受体 (ER) 介导，但 ER 与 AR 信号在男性中的相对作用尚不清楚（Lindzey 等人，1998 年；Wersinger 等人，1999 年）。因此，本综述将重点关注女性中的雌激素信号。
