Circulating levels of oestrogen are known to modulate autonomic function via conventional nuclear oestrogen receptors (ERα and ERβ) localised in several areas of the brain(1,2). Recently several lines of evidence suggest that the orphan G protein-coupled receptor GPR30 may also act as a cytoplasmic oestrogen receptor and is expressed throughout the brain (3). This study investigates the expression and localisation of GPR30 in the medulla oblongata of male and female rats by a combination of quantitative RT-PCR (qPCR) and immunohistochemistry, focusing on the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM). Changes in GPR30 expression were examined throughout the oestrus cycle, after ovariectomy and in spontaneously hypertensive rats (SHR). In brains fixed with 4% paraformaldehyde by perfusion under anaesthesia (Isofluorane 5% by inhalation, n=4), immunoreactivity for GPR30 was typically punctate in the perinuclear cytoplasm and proximal dendrites of neurones in most divisions of the medulla oblongata, including the NTS and other areas associated with autonomic pathways. Very intense labelling was present in scattered large neurones of the ventral parapyramidal reticular formation. Double labelling localised GPR30 immunoreactivity to a variety of identified neuronal phenotypes, including cholinergic (dorsal vagal and cranial nuclei), serotonergic (raphé nuclei), catecholaminergic (NTS and VLM) and nitrergic (NTS & VLM). In tissue micropunches of NTS and VLM, qPCR (n=6) revealed variations in GPR30 mRNA expression across the oestrous cycle. In both areas expression in males was significantly lower than that in females during oestrus (ANOVA, p<0.01). In the NTS, GPR30 expression was significantly increased in proestrus (p<0.05) compared to metoestrus, and oestrus compared to metoestrus (p<0.01) or dioestrus (p<0.05). A similar result was observed for the VLM with significantly higher levels of GPR30 mRNA in proestrus (p<0.05) and oestrus (p<0.01) compared to metoestrus, and in oestrus compared to dioestrus (p<0.05). In surgically ovariectomised (OVX) rats (anaesthesia as above) expression in both NTS and VLM was increased in the OVX females compared to the sham-operated animals. GPR30 expression in the VLM was significantly greater than in shams during the low oestrogen, met/dioestrus phases (p<0.05). In the male SHR, significantly higher levels of GPR30 expression were seen in the NTS compared to normotensive Wistar-Kyoto controls (p<0.01). These observations are consistent with the view that GPR30 expressed on neuronal membranes may have a role as a rapid transducer responding to plasma oestrogen levels to modulate the activity of central nervous pathways that regulate autonomic function.