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

The Progesterone receptor A isoform (PR-A) is a ligand-dependent transcription factor and one of the two major isoforms of the human progesterone receptor, encoded by the PGR gene (UniProt P06401). PR-A is a truncated version of the PR-B isoform, lacking the N-terminal 164 amino acids, which leads to its unique role as a trans-dominant repressor of PR-B and other steroid receptors in certain cellular contexts (PMID: 10657340). It is essential for female fertility, specifically mediating the progestational effects required for ovulation and uterine receptivity (NCBI Gene ID: 5241). In disease, an imbalance in the PR-A/PR-B ratio is frequently observed in breast and endometrial cancers, where PR-A predominance often correlates with poorer prognosis or resistance to certain endocrine therapies (PMID: 15155153). Therapeutic targeting of PR-A involves agonists like progesterone for pregnancy support and antagonists or selective progesterone receptor modulators (SPRMs) like mifepristone and ulipristal acetate for conditions such as uterine fibroids and emergency contraception (DrugBank DB00396, DB00347).

Other names

PGRNuclear receptor subfamily 3 group C member 3NR3C3PR-APRA

PR-A acts as a ligand-activated transcription factor. Upon binding to progesterone or synthetic progestins, it undergoes a conformational change, dimerizes, and translocates to the nucleus where it binds to progesterone response elements (PREs) to modulate gene expression (UniProt P06401). Notably, PR-A can also inhibit the transcriptional activity of PR-B and other nuclear receptors through a mechanism involving the recruitment of co-repressors (PMID: 10657340).