Progesterone receptor isoform A (PR-A) (PR-A)

Progesterone receptor isoform A (PR-A) is a key member of the nuclear receptor superfamily and one of the two primary isoforms of the human progesterone receptor, both encoded by the PGR gene (UniProt P06401). It is a truncated version of the PR-B isoform, lacking the N-terminal 164 amino acids, which results in distinct functional properties (Shao, 2013). While PR-B typically acts as a strong transcriptional activator, PR-A often functions as a ligand-dependent transdominant repressor of other steroid receptors, including PR-B and the estrogen receptor (Mote et al., 2002). This inhibitory role is crucial for maintaining hormonal balance and regulating reproductive processes such as uterine development, fertility, and mammary gland morphogenesis (Boonyaratanakornkit et al., 2018). In clinical contexts, an imbalance in the PR-A to PR-B ratio is a significant biomarker for disease progression; for instance, elevated PR-A levels are frequently linked to progesterone resistance and poor prognosis in breast and endometrial cancers (Shao, 2013; PubMed 38834744). Therapeutic strategies targeting PR-A involve a variety of ligands, including progestins, antiprogestogens like mifepristone, and selective progesterone receptor modulators (SPRMs) (PubMed 18076104). These drugs are utilized to treat hormone-dependent malignancies, endometriosis, and uterine fibroids by modulating the receptor's transcriptional activity and its interaction with coregulators.

Other names

PR-APgR-APGR isoform ANuclear receptor subfamily 3 group C member 3 isoform AhPR-A

Progesterone receptor isoform A (PR-A) functions as a ligand-dependent transcription factor that primarily acts as a transdominant repressor of other steroid hormone receptors, including the PR-B isoform and the estrogen receptor (UniProt P06401; Shao, 2013). Upon binding to a ligand, PR-A undergoes a conformational change, dimerizes, and binds to progesterone response elements (PREs) in the promoter regions of target genes (GeneCards). It then recruits corepressors, such as NCOR2 (SMRT), to inhibit gene transcription, thereby modulating physiological processes in the uterus and mammary glands, as well as pathological processes in hormone-dependent cancers (Boonyaratanakornkit et al., 2018).