Inserra Pablo Ignacio Felipe, Charif Santiago Elías, Di Giorgio Noelia Paula, Saucedo Lucía, Schmidt Alejandro Raúl, Fraunhoffer Nicolas, Halperin Julia, Gariboldi María Constanza, Leopardo Noelia Paola, Lux-Lantos Victoria, Gonzalez Candela Rocío, Vitullo Alfredo Daniel, Dorfman Verónica Berta
Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y Diagnóstico (CEBBAD), Universidad Maimónides, Hidalgo 775 6to piso, C1405BCK, Ciudad Autónoma de Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
J Mol Histol. 2017 Jun;48(3):259-273. doi: 10.1007/s10735-017-9715-6. Epub 2017 Mar 19.
Gonadotropin-releasing hormone (GnRH) is the key regulator of the hypothalamic-pituitary-gonadal axis. Estradiol (E) affects GnRH synthesis and delivery. Hypothalamic estrogen receptors (ER) modulate GnRH expression acting as transcription factors. The South American plains vizcacha, Lagostomus maximus, is able to ovulate up to 800 oocytes per reproductive cycle, and shows continuous folliculogenesis with pre-ovulatory follicle formation and an ovulatory event at mid-gestation. The aim of this work was to analyze the hypothalamic expression of ER in the vizcacha at different gestational time-points, and its relationship with GnRH expression, serum luteinizing hormone (LH) and E. The hormonal pattern of mid-gestating vizcachas was comparable to ovulating-females with significant increases in GnRH, LH and E. Hypothalamic protein and mRNA expression of ERα varied during pregnancy with a significant increase at mid-gestation whereas ERβ mRNA expression did not show significant variations. Hypothalamic immunolocalization of ERα was observed in neurons of the diagonal band of Brocca, medial preoptic area (mPOA), periventricular, suprachiasmatic, supraoptic (SON), ventromedial, and arcuate nuclei, and medial eminence, with a similar distribution throughout gestation. In addition, all GnRH neurons of the mPOA and SON showed ERα expression with no differences across the reproductive status. The correlation between GnRH and ERα at mid-gestation, and their co-localization in the hypothalamic neurons of the vizcacha, provides novel information compared with other mammals suggesting a direct action of estrogen as part of a differential reproductive strategy to assure GnRH synthesis during pregnancy.
促性腺激素释放激素（GnRH）是下丘脑 - 垂体 - 性腺轴的关键调节因子。雌二醇（E）影响GnRH的合成与释放。下丘脑雌激素受体（ER）作为转录因子调节GnRH的表达。南美草原 vizcacha（Lagostomus maximus）每个生殖周期能够排出多达800个卵母细胞，并表现出持续的卵泡发生，包括排卵前卵泡的形成以及妊娠中期的排卵事件。本研究的目的是分析不同妊娠时间点 vizcacha 下丘脑 ER 的表达情况，及其与GnRH表达、血清促黄体生成素（LH）和E的关系。妊娠中期 vizcacha 的激素模式与排卵雌性相似，GnRH、LH和E显著增加。ERα的下丘脑蛋白和mRNA表达在孕期有所变化，在妊娠中期显著增加，而ERβ mRNA表达未显示出显著变化。在布罗卡斜带、内侧视前区（mPOA）、室周、视交叉上、视上（SON）、腹内侧和弓状核以及内侧隆起的神经元中观察到ERα的下丘脑免疫定位，在整个妊娠期间分布相似。此外，mPOA和SON的所有GnRH神经元均显示ERα表达，在不同生殖状态下无差异。与其他哺乳动物相比，妊娠中期GnRH与ERα之间的相关性及其在下丘脑神经元中的共定位提供了新的信息，表明雌激素作为一种不同生殖策略的一部分具有直接作用，以确保孕期GnRH的合成。
