Progesterone receptor A

The progesterone receptor A (PR-A) is one of three known isoforms of the progesterone receptor (PR), the main biological target of the endogenous progestogen sex hormone progesterone.^[1][2] The other isoforms of the PR include the PR-B and PR-C.^[1][2]

The AlphaFold predictive structure of the entire progesterone receptor with the region unique to isoform A highlighted in purple. Amino acids 1-164 are seen in grey as they are not included in isoform A. AlphaFold Identifier: AF-P060401-F

PR-A is 164 residues shorter than PR-B in humans^[3] and anywhere from 128-165 residues shorter in other organisms.^[4] Each isoform binds its natural ligand, progesterone, but also demonstrates the ability to bind a number of other agonists including norethindrone, a synthetic progestin.^[5]

The crystallographic structure of the ligand-binding domain which is common to both isoforms A and B in its dimerized conformation (purple). Dimerization will only occur when a ligand is bound. The study which yielded this structure (Maduass et al. 2004) used agonists mometasone fuorate and norethindrone (grey) to induce dimerization. PBD Identifier: 1SQN

Expression and overexpression

PR-A and PR-B are generally expressed in equal ratios,^[3] but PR-A is expressed in larger amounts in uterine stromal cells normally.^[6] A spike in PR-A expression in the myometrium has been observed to initiate parturition in placental mammals.^[7]

PR-A is the isoform most commonly observed to be overexpressed in human breast cancer and patients with PR-A rich carcinomas, as opposed to patients with PR-B rich carcinomas, have faster recurrence rates.^[8]

See also

• Membrane progesterone receptor