Fig 2: Schematic representation of Nk3R–GPER and Nk3R–GPAR in the dorsal hippocampus and the medial prefrontal cortex. Males are represented in blue on the left and females in green on the right. The percentage of positive cells is represented with the sign +. ++ indicates a medium expression (25–75%) and +++ indicates a high proportion (< 75%)

Fig 3: Heterodimerization of neurokinin 3 receptor with membrane sex hormones receptors. A Quantification of heterodimerization Nk3R with G-protein androgen receptor (GPAR) and G-protein estrogen receptor (GPER) in male and female mice during proestrus. CG cingulate cortex, IL infralimbic cortex, PrL prelimbic cortex, CA1 field CA1 of hippocampus, CA3 field CA3 of hippocampus, DG dentate gyrus. Data are mean ± SEM. Datasets were analyzed using two-way ANOVA. **p < 0.01, ***p < 0.001. B Representative confocal images of the previously reported quantification. Scale bar = 20 µm

Fig 4: Expression of GPER in endometrial cancer tissue and adjacent control endometrium at the mRNA and protein levels. (A) Before-and-after graphs show the normalized expression levels of the GPER gene variants 2, and variants 3 and 4 (as indicated) in control endometrial tissue (Control) and the corresponding EC tissue (Tumor). The levels of gene expression are on a logarithmic scale. (B) ECL detection of GPER. 18 paired samples were analyzed using anti-GPER antibodies (HPA027052, Sigma-Aldrich, Cat. #: HPA027052, Lot: A61748) in the control endometrial tissue (C) and EC tissue (T). Placenta (P) was used as the positive control. Below, the detection of GAPDH used for quantification. Before-and-after graph shows the GPER protein levels in the control and EC tissue. (D) IHC staining in representative paired adjacent control endometrial tissue (C38) and EC tissue (T38) for GPER. In the negative controls (Control), the primary antibodies were replaced with serum of the same animal species (rabbit). Anti-GPER antibodies were validated by Western blotting analysis (Supplementary Figure S7, Supplementary Table S5).

Fig 5: GPER is not expressed in normal pancreatic ductal cells, and G-1 is not active. (A) GPER Western blot of lysates from human PDAC cell lines and HPDE cells. (B) GPER Western blot of lysates from murine PDAC cell lines and wild-type murine pancreatic ductal organoids. (C) Proliferation of wild-type pancreatic ductal organoids treated with 250 nmol/L G-1, n = 5 per group. (D) Brightfield images of wild-type pancreatic ductal organoids treated with G-1. WT, wild-type.