Expression Pattern of G Protein-Coupled Receptor 30 in LacZ Reporter Mice

Abstract

Multiple reports implicated the function of G protein-coupled receptor (GPR)-30 with nongenomic effects of estrogen, suggesting that GPR30 might be a G-protein coupled estrogen receptor. However, the findings are controversial and the expression pattern of GPR30 on a cell type level as well as its function in vivo remains unclear. Therefore, the objective of this study was to identify cell types that express Gpr30 in vivo by analyzing a mutant mouse model that harbors a lacZ reporter (Gpr30-lacZ) in the Gpr30 locus leading to a partial deletion of the Gpr30 coding sequence. Using this strategy, we identified the following cell types expressing Gpr30: 1) an endothelial cell subpopulation in small arterial vessels of multiple tissues, 2) smooth muscle cells and pericytes in the brain, 3) gastric chief cells in the stomach, 4) neuronal subpopulations in the cortex as well as the polymorph layer of the dentate gyrus, 5) cell populations in the intermediate and anterior lobe of the pituitary gland, and 6) in the medulla of the adrenal gland. In further experiments, we aimed to decipher the function of Gpr30 by analyzing the phenotype of Gpr30-lacZ mice. The body weight as well as fat mass was unchanged in Gpr30-lacZ mice, even if fed with a high-fat diet. Flow cytometric analysis revealed lower frequencies of T cells in both sexes of Gpr30-lacZ mice. Within the T-cell cluster, the amount of CD62L-expressing cells was clearly reduced, suggesting an impaired production of T cells in the thymus of Gpr30-lacZ mice.

Estrogen receptor (ER) expression and function in the pregnant human myometrium: estradiol via ERα activates ERK1/2 signaling in term myometrium

“…On balance, the current weight of evidence suggests that GPR30 is most likely a bona fide ER, and our data are similar to a recent report showing that GPR30 mRNA and protein are present in the term pregnant human myometrium (Maiti et al 2011). The role of GPR30 in reproduction and especially uterine function during pregnancy is unknown; however, GPR30 knockout mice have unimpaired fertility, retain normal uterine estrogenic responses, and appear to have normal pregnancies and parturition (Wang et al 2008, Isensee et al 2009, Otto et al 2009, Windahl et al 2009. Current data therefore suggest that the role of GPR30 in mediating estrogen actions in the pregnant myometrium is minimal.…”

In Vivo Functions of GPR30/GPER-1, a Membrane Receptor for Estrogen: From Discovery to Functions In Vivo

“…The deletion of GPR30 from mice attenuates the G-1-induced relax of the carotid arteries, and there is no observed sex difference in the reductive effect of GPR30 [30]. The expression of the GPR30 mRNa is observed in the endothelium of the peripheral vessels of Lacz-introduced mice [19]. The production of No by E2 in endothelial cells may be mediated using the breast cancer cell line McF-7 and SkBr (Fig.…”

“…up to now, data on the expression of the GPR30 mRNa in tissues has not necessarily produced a consensus result, although various methods were used including northern blotting, RT-PcR methods, and RNase protection assays [9,10,[18][19][20][21] (Table 1). The mRNa for GPR30 appears to be expressed extensively in most tissues as judged from the overall reports.…”

“…There are reports that GPR30 localizes in both the endoplasmic reticulum and Golgi apparatus [12,17], Recently, isensee et al have succeeded in producing GPR30 ko mice with a Lacz gene introduced downstream of the GPR30 promoter, causing research in this field to be greatly advanced [19]. In these mice, GPR30 expression is limited to the blood vessels in the brain and the arteries in skeletal muscles and adipocytes.…”

“…other than blood vessels, the data obtained from Laczexpressing mice indicates the GPR30 mRNa to be highly inducible in digestive tissues including the stomach, pancreas, and duodenum. an interesting observation that the expression of GPR30 is mainly observed in the exocrine cells of the digestive tissues has been obtained in mice [19]. The expression of GPR30 in sexual organs has not been analyzed in detail up to now.…”