Comparative Analysis of the Progesterone Receptor Interactome in the Human Ovarian Granulosa Cell Line KGN and Other Female Reproductive Cells.

Abstract

The nuclear steroid hormone receptor progesterone receptor (PGR) is expressed in granulosa cells in the ovarian follicle in a tightly regulated pattern in response to the surge of luteinizing hormone (LH) that stimulates ovulation. PGR plays a critical role in mediating ovulation in response to LH, however, the mechanism for this is still unknown. We performed immunoprecipitation-mass spectrometry using the KGN human granulosa cell line expressing the primary PGR isoforms PGR-A or PGR-B, to identify novel interacting proteins that regulate PGR function in these ovary-specific target cells. Proteomic analysis revealed protein interactions with both PGR isoforms that were gained (e.g., transcriptional coactivators) or lost (e.g., chaperone proteins) in response to the PGR agonist R5020. Additionally, isoform-specific interactions, including different families of transcriptional regulators, were identified. Comparison with published datasets of PGR-interacting proteins in human breast cancer cell lines and decidualized endometrial stromal cells demonstrated a remarkable number of tissue-specific interactions, shedding light on how PGR can maintain diverse functions in different tissues. In conclusion, we provide a comprehensive novel dataset of the PGR interactome in previously unstudied ovarian cells and offer new insights into ovary-specific PGR transcriptional mechanisms.