Pgr, short for progesterone receptor, is a member of the nuclear receptor superfamily. Progesterone, a key steroid hormone, exerts its physiological effects by binding to Pgr. Pgr is involved in regulating functions of reproductive and non-reproductive tissues, and plays a crucial role in female reproduction-related processes such as embryo implantation, ovulation, and endometrial receptivity [2,3,5].

In breast cancer, PGR-KITLG signaling drives a tumor-mast cell regulatory feedback. In HR(+) breast cancer, PGR transcriptionally upregulates KITLG, a mast cell growth factor, which in turn increases the production of MC-derived granulin (GRN). GRN attenuates TNFα-induced apoptosis in breast cancer cells. Disrupting PGR-KITLG signaling enhances the sensitivity of HR(+) breast cancer cells to MC-induced apoptosis [1]. In the endometrium, uterine-specific Arid1a knockout mice showed infertility due to loss of epithelial PGR signaling, and ARID1A and PGR proteins interact and show a positive correlation in endometriosis [4]. Conditional deletion of Mettl3 in the female reproductive tract using a Pgr-Cre mouse line led to implantation failure and defective uterine receptivity, as Mettl3 is essential for normal progesterone signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA [3].

In summary, Pgr is vital for normal female reproductive processes like embryo implantation, ovulation, and endometrial receptivity. Through gene-knockout models, it has been revealed that Pgr also plays a significant role in breast cancer and endometriosis-related infertility, providing insights into potential therapeutic targets for these diseases.