Progesterone receptor (isoform C) (PR-C)

The Progesterone receptor C (PR-C) is a truncated, 38 kDa isoform of the human progesterone receptor (PGR), distinct from the more commonly studied PR-A and PR-B isoforms (UniProt P06401). It is generated through alternative translation initiation or mRNA splicing and lacks the N-terminal transactivation domains and the DNA-binding domain, while retaining the C-terminal ligand-binding domain (LBD) and the hinge region (PubMed 11095991). Because it lacks the ability to bind DNA directly, PR-C functions primarily as a modulator of progesterone signaling, often acting as a dominant-negative regulator by sequestering progesterone or forming heterodimers with PR-A and PR-B (PubMed 16461641). PR-C expression is significantly increased in the human myometrium during labor, where it is thought to contribute to functional progesterone withdrawal by interfering with the pro-gestational effects of PR-B (PubMed 16461641). In oncology, the ratio of PR isoforms, including PR-C, is investigated as a factor in the progression of hormone-dependent breast cancers and their response to endocrine therapy (PubMed 11095991). Drugs that target the progesterone receptor, such as the antagonist mifepristone or various synthetic progestins, bind to the LBD of PR-C, potentially altering its inhibitory or modulatory functions (StatPearls NBK558960).

Other names

PGR isoform C38 kDa progesterone receptorTruncated progesterone receptorProgesterone receptor C

Ligand binding to the C-terminal domain, which modulates the activity of other progesterone receptor isoforms (PR-A and PR-B) through ligand sequestration or heterodimerization, thereby influencing progesterone-mediated gene transcription.