Progesterone receptor isoform B (PR-B) (PR-B)

The Progesterone receptor isoform B (PR-B) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily, encoded by the PGR gene [1, 2]. It is the full-length version of the receptor, distinguished from the shorter PR-A isoform by an additional 164-amino acid N-terminal segment known as the B-upstream segment (BUS) [7, 13]. This unique region contains the AF3 transactivation domain, which allows PR-B to function as a potent transcriptional activator of progesterone-responsive genes involved in female reproductive development, mammary gland morphogenesis, and pregnancy maintenance [3, 7, 10]. In clinical oncology, PR-B is a critical target; its downregulation is linked to progesterone resistance in endometrial cancer, while its overexpression or an imbalanced PR-A:PR-B ratio is associated with increased proliferation in breast and prostate cancers [1, 11, 16]. Therapeutic strategies targeting PR-B include the use of synthetic progestins for contraception and hormone replacement, as well as selective progesterone receptor modulators (SPRMs) like mifepristone and ulipristal for treating uterine fibroids and endometriosis [4, 13, 14].

Other names

hPR-BPGR-BProgesterone receptor BFull-length progesterone receptor

Ligand binding to PR-B induces a conformational change, dimerization, and translocation to the nucleus, where the receptor binds to Progesterone Response Elements (PREs) in target gene promoters [3, 7, 11]. PR-B specifically utilizes its unique N-terminal B-upstream segment (BUS), which contains the AF3 transactivation domain, to recruit coactivators like SRC-1 and strongly activate transcription [7, 10]. Additionally, PR-B mediates rapid non-genomic signaling by interacting with cytoplasmic proteins such as Src kinase to activate the MAPK pathway, promoting cell proliferation [3, 6, 11].