Spary Emma J, Chapman Sally E, Sinfield John K, Maqbool Azhar, Kaye Jean, Batten Trevor F C
Division of Cardiovascular and Neuronal Remodelling, LIGHT Institute, University of Leeds, Leeds, UK.
Neurosignals. 2013;21(1-2):14-27. doi: 10.1159/000333296. Epub 2012 Feb 23.
Oestrogen influences autonomic function via actions at classical nuclear oestrogen receptors α and β in the brain, and recent evidence suggests the orphan G protein-coupled receptor GPR30 may also function as a cytoplasmic oestrogen receptor. We investigated the expression of GPR30 in female rat brains throughout the oestrous cycle and after ovariectomy to determine whether GPR30 expression in central autonomic nuclei is correlated with circulating oestrogen levels. In the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM) and periaqueductal gray (PAG) GPR30 mRNA, quantified by real-time PCR, was increased in proestrus and oestrus. In ovariectomised (OVX) rats, expression in NTS and VLM appeared increased compared to metoestrus, but in the hypothalamic paraventricular nucleus and PAG lower mRNA levels were seen in OVX. GPR30-like immunoreactivity (GPR30-LI) colocalised with Golgi in neurones in many brain areas associated with autonomic pathways, and analysis of numbers of immunoreactive neurones showed differences consistent with the PCR data. GPR30-LI was found in a variety of transmitter phenotypes, including cholinergic, serotonergic, catecholaminergic and nitrergic neurones in different neuronal groups. These observations support the view that GPR30 could act as a rapid transducer responding to oestrogen levels and thus modulate the activity of central autonomic pathways.
雌激素通过作用于大脑中经典的核雌激素受体α和β来影响自主神经功能,最近有证据表明,孤儿G蛋白偶联受体GPR30也可能作为一种细胞质雌激素受体发挥作用。我们研究了雌性大鼠大脑在整个发情周期以及卵巢切除后的GPR30表达,以确定中枢自主神经核中的GPR30表达是否与循环雌激素水平相关。通过实时PCR定量分析,孤束核(NTS)、延髓腹外侧区(VLM)和导水管周围灰质(PAG)中的GPR30 mRNA在动情前期和动情期有所增加。在卵巢切除(OVX)的大鼠中,与间情期相比,NTS和VLM中的表达似乎增加了,但在OVX大鼠的下丘脑室旁核和PAG中,mRNA水平较低。GPR30样免疫反应性(GPR30-LI)在许多与自主神经通路相关的脑区的神经元中与高尔基体共定位,对免疫反应性神经元数量的分析显示出与PCR数据一致的差异。在不同神经元群体的多种递质表型中发现了GPR30-LI,包括胆碱能、5-羟色胺能、儿茶酚胺能和一氧化氮能神经元。这些观察结果支持这样一种观点,即GPR30可能作为一种快速传感器对雌激素水平作出反应,从而调节中枢自主神经通路的活动。