Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715.
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715;
Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):13804-13809. doi: 10.1073/pnas.1716097115. Epub 2017 Dec 11.
Negative and positive feedback effects of ovarian 17β-estradiol (E) regulating release of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) are pivotal events in female reproductive function. While ovarian feedback on hypothalamo-pituitary function is a well-established concept, the present study shows that neuroestradiol, locally synthesized in the hypothalamus, is a part of estrogen's positive feedback loop. In experiment 1, E benzoate-induced LH surges in ovariectomized female monkeys were severely attenuated by systemic administration of the aromatase inhibitor, letrozole. Aromatase is the enzyme responsible for synthesis of E from androgens. In experiment 2, using microdialysis, GnRH and kisspeptin surges induced by E benzoate were similarly attenuated by infusion of letrozole into the median eminence of the hypothalamus. Therefore, neuroestradiol is an integral part of the hypothalamic engagement in response to elevated circulating E Collectively, we will need to modify the concept of estrogen's positive feedback mechanism.
卵巢 17β-雌二醇（E）对促性腺激素释放激素（GnRH）和黄体生成素（LH）释放的负反馈和正反馈效应是女性生殖功能的关键事件。虽然卵巢对下丘脑-垂体功能的反馈是一个既定的概念，但本研究表明，神经雌二醇是在大脑中局部合成的，是雌激素正反馈循环的一部分。在实验 1 中，全身性给予芳香化酶抑制剂来曲唑严重削弱了苯甲酸雌二醇诱导的去卵巢雌性猴子的 LH 激增。芳香化酶是负责将雄激素转化为 E 的酶。在实验 2 中，使用微透析技术，用来曲唑输注到下丘脑的正中隆起也同样削弱了由苯甲酸雌二醇诱导的 GnRH 和 kisspeptin 激增。因此，神经雌二醇是大脑对循环中 E 升高反应的一个组成部分。
综上所述，我们需要修改雌激素正反馈机制的概念。
