Sakamoto Hirotaka, Matsuda Ken-ichi, Hosokawa Koji, Nishi Mayumi, Morris John F, Prossnitz Eric R, Kawata Mitsuhiro
Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Endocrinology. 2007 Dec;148(12):5842-50. doi: 10.1210/en.2007-0436. Epub 2007 Sep 13.
The regulatory actions of estrogens on magnocellular oxytocin (OT) neurons of the paraventricular and supraoptic nuclei are well documented. Although the expression and distribution of nuclear estrogen receptor-beta, but not estrogen receptor-alpha, in the OT neuron has been described, the nuclear receptors may not explain all aspects of estrogen function in the hypothalamic OT neuron. Recently a G protein-coupled receptor (GPR) for estrogens, GPR30, has been identified as a membrane-localized estrogen receptor in several cancer cell lines. In this study, we therefore investigated the expression and localization of GPR30 in magnocellular OT neurons to understand the mode of rapid estrogen actions within these neurons. Here we show that, in the paraventricular nucleus and supraoptic nucleus, GPR30 is expressed in magnocellular OT neurons at both mRNA and protein levels but is not expressed in vasopressin neurons. Specific markers for intracellular organelles and immunoelectron microscopy revealed that GPR30 was localized mainly in the Golgi apparatus of the neurons but could not be detected at the cell surface. In addition, the expression of GPR30 is also detected in the neurohypophysis. These results suggest that GPR30 may serve primarily as a nongenomic transducer of estrogen actions in the hypothalamo-neurohypophyseal system.
雌激素对室旁核和视上核的大细胞催产素（OT）神经元的调节作用已有充分记载。尽管已描述了OT神经元中核雌激素受体-β而非雌激素受体-α的表达和分布，但核受体可能无法解释雌激素在下丘脑OT神经元中功能的所有方面。最近，一种雌激素的G蛋白偶联受体（GPR），即GPR30，已被鉴定为几种癌细胞系中的膜定位雌激素受体。因此，在本研究中，我们研究了GPR30在大细胞OT神经元中的表达和定位，以了解这些神经元内雌激素快速作用的模式。我们在此表明，在室旁核和视上核中，GPR30在大细胞OT神经元中以mRNA和蛋白质水平表达，但在加压素神经元中不表达。细胞内细胞器的特异性标记物和免疫电子显微镜显示，GPR30主要定位于神经元的高尔基体，但在细胞表面未检测到。此外，在神经垂体中也检测到了GPR30的表达。这些结果表明，GPR30可能主要作为下丘脑-神经垂体系统中雌激素作用的非基因组转导器。
