The South American plains vizcacha, Lagostomus maximus, is the only mammal described so far that shows expression of estrogen receptors (ERs) and progesterone receptors (PRs) in gonadotropin-releasing hormone (GnRH) neurons. This animal therefore constitutes an exceptional model for the study of the effect of steroid hormones on the modulation of the hypothalamic-pituitary-ovarian (HPO) axis. By using both in vivo and ex vivo approaches, we have found that pharmacological doses of progesterone (P4) and estradiol (E2) produced an inhibition in the expression of hypothalamic GnRH, while physiological doses produced a differential effect on the pulsatile release frequency or genomic expression of GnRH. Our ex vivo experiment indicates that a short-term effect of E2 modulates the frequency of GnRH release pattern that would be associated with membrane ERs. On the other hand, our in vivo approach suggests that a long-term effect of E2, acting through the classical nuclear ERs-PRs pathway, would produce the modification of GnRH mRNA expression during the GnRH pre-ovulatory surge. Particularly, P4 induced a rise in GnRH mRNA expression and protein release with a decrease in its release frequency. These results suggest different levels of action of steroid hormones on GnRH modulation. We conclude that the fine action of E2 and P4 constitute the key factor to enable the hypothalamic activity during the pregnancy of this mammal.

中文翻译：

---

雌二醇和孕酮的关键作用是在南美平原比格（Lagostomus maximus）的妊娠期使GnRH传递。

南美平原比斯卡恰（Lagostomus maximus）是迄今为止描述的唯一一种在促性腺激素释放激素（GnRH）神经元中显示雌激素受体（ERs）和孕激素受体（PRs）表达的哺乳动物。因此，该动物构成了研究类固醇激素对下丘脑-垂体-卵巢（HPO）轴调节作用的出色模型。通过体内和体外方法，我们发现药理剂量的孕酮（P4）和雌二醇（E2）对下丘脑GnRH的表达产生抑制作用，而生理剂量对脉动释放频率或基因组产生不同的影响GnRH的表达。我们的离体实验表明，E2的短期作用会调节与膜ER相关的GnRH释放模式的频率。另一方面，我们的体内方法表明，E2的长期作用（通过经典核ERs-PRs途径起作用）将在排卵前GnRH激增期间产生GnRH mRNA表达的修饰。特别地，P4诱导GnRH mRNA表达和蛋白质释放增加，其释放频率降低。这些结果表明类固醇激素对GnRH调节的作用水平不同。我们得出的结论是，E2和P4的良好作用是使该哺乳动物怀孕期间下丘脑活动的关键因素。通过经典的核ERs-PRs途径发挥作用，将在排卵前GnRH激增期间产生GnRH mRNA表达的修饰。特别是，P4诱导GnRH mRNA表达和蛋白质释放增加，其释放频率降低。这些结果表明类固醇激素对GnRH调节的作用水平不同。我们得出的结论是，E2和P4的良好作用是使该哺乳动物怀孕期间下丘脑活动的关键因素。通过经典的核ERs-PRs途径起作用，将在排卵前GnRH激增期间产生GnRH mRNA表达的修饰。特别是，P4诱导GnRH mRNA表达和蛋白质释放增加，其释放频率降低。这些结果表明类固醇激素对GnRH调节的作用水平不同。我们得出的结论是，E2和P4的良好作用是使该哺乳动物怀孕期间下丘脑活动的关键因素。