The negative feedback actions of progesterone on gonadotropin-releasing hormone secretion are transduced by the classical progesterone receptor.
The negative feedback actions of progesterone on gonadotropin-releasing hormone secretion are transduced by the classical progesterone receptor.
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黄体酮对促性腺激素释放激素分泌的负反馈作用是由经典黄体酮受体转导的。
DOI：
10.1073/pnas.95.18.10978
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发表时间：
1998
影响因子：
11.1
通讯作者：
Caraty,A
中科院分区：
文献类型：
--
作者：
Skinner,DC;Evans,NP;Delaleu,B;Goodman,RL;Bouchard,P;Caraty,A
与其他物种一样，孕酮(P)能有效抑制母羊的促性腺激素释放激素（GnRH）分泌，但这种作用背后的神经机制尚不清楚。使用无雌激素(E)的绵羊模型，我们研究了GnRH和黄体生成素（LH）对急性循环P浓度的反应，以及这种反应是否由核P受体介导。在外源性P存在（P治疗开始于8天前）的情况下，同时采集垂体门静脉和颈静脉血液样本，时间为36小时：0-12小时；12-24小时，取出P植入物；24-36小时，重新植入P植入物。P去除导致GnRH脉冲频率显著快速增加，在两个脉冲（175分钟）内可检测到。P插入抑制GnRH脉冲频率更快：在一个脉冲（49分钟）内检测到效果。LH脉动也同样被调制。接下来的两个实验表明，P的这些作用是由核P受体介导的，因为脑室内注入P抑制了LH的释放，而通过A型γ-氨基丁酸受体作用的3α-羟基-5α-孕-20- 1没有作用，P受体拮抗剂RU486预处理阻断了P抑制LH的能力。我们最后的研究表明，P通过E依赖系统发挥其对GnRH的急性抑制作用，因为P对长期E剥夺后失去的LH分泌的影响在E治疗2周后恢复。因此，我们证明P通过e依赖的核P受体系统急性抑制GnRH。
Progesterone (P) powerfully inhibits gonadotropin-releasing hormone (GnRH) secretion in ewes, as in other species, but the neural mechanisms underlying this effect remain poorly understood. Using an estrogen (E)-free ovine model, we investigated the immediate GnRH and luteinizing hormone (LH) response to acute manipulations of circulating P concentrations and whether this response was mediated by the nuclear P receptor. Simultaneous hypophyseal portal and jugular blood samples were collected over 36 hr: 0–12 hr, in the presence of exogenous P (P treatment begun 8 days earlier); 12–24 hr, P implant removed; 24–36 hr, P implant reinserted. P removal caused a significant rapid increase in the GnRH pulse frequency, which was detectable within two pulses (175 min). P insertion suppressed the GnRH pulse frequency even faster: the effect detectable within one pulse (49 min). LH pulsatility was modulated identically. The next two experiments demonstrated that these effects of P are mediated by the nuclear P receptor since intracerebroventricularly infused P suppressed LH release but 3α-hydroxy-5α-pregnan-20-one, which operates through the type A γ-aminobutyric acid receptor, was without effect and pretreatment with the P-receptor antagonist RU486 blocked the ability of P to inhibit LH. Our final study showed that P exerts its acute suppression of GnRH through an E-dependent system because the effects of P on LH secretion, lost after long-term E deprivation, are restored after 2 weeks of E treatment. Thus we demonstrate that P acutely inhibits GnRH through an E-dependent nuclear P-receptor system.