Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Jan;121(1):14-9.
doi: 10.1016/j.pharmthera.2008.09.006. Epub 2008 Nov 1.

PGRMC1 (progesterone receptor membrane component 1): a targetable protein with multiple functions in steroid signaling, P450 activation and drug binding

Hannah J Rohe  1 , Ikhlas S Ahmed, Katherine E Twist, Rolf J Craven
Affiliations
Review

PGRMC1 (progesterone receptor membrane component 1): a targetable protein with multiple functions in steroid signaling, P450 activation and drug binding

Hannah J Rohe et al. Pharmacol Ther. 2009 Jan.

Abstract

Hormone signaling is important in a number of disease states, and hormone receptors are effective therapeutic targets. PGRMC1 (progesterone receptor membrane component 1) is a member of a multi-protein complex that binds to progesterone and other steroids, as well as pharmaceutical compounds. In spite of its name, PGRMC1 shares homology with cytochrome b5-related proteins rather than hormone receptors, and heme binding is the sole biochemical activity of PGRMC1. PGRMC1 and its homologues regulate cholesterol synthesis by activating the P450 protein Cyp51/lanosterol demethylase, and the cholesterol synthetic pathway is an important target in cardiovascular disease and in treating infections. PGRMC1 binding partners include multiple P450 proteins, PAIR-BP1, Insig, and an uncharacterized hormone/drug-binding protein. PGRMC1 is induced in a spectrum of cancers, where it promotes cell survival and damage resistance, and PGRMC1 is also expressed in the nervous system and tissues involved in drug metabolism, cholesterol synthesis and hormone synthesis and turnover. One of the appealing features of PGRMC1 and its associated protein complex is its affinity for steroids and drugs. Together with its biological role in promoting tumor survival, PGRMC1 is an attractive target for therapeutic intervention in cancer and related malignancies.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Conserved and divergent functions of PGRMC1 proteins in evolution. In unicellular organisms, Dap1 binds and activates the P450 protein Cyp51, promoting sterol synthesis and damage resistance. In mammals, PGRMC1 binds to multiple P450 proteins, suggesting additional functions in drug and hormone metabolism. PGRMC1 also binds to an unknown progesterone binding protein, to PAIR-BP1 and to Insig and SCAP.
Fig. 2
Fig. 2
A model for the structure of residues 71-171 of PGRMC1. Asterisks indicate identical residues between PGRMC1 and its yeast homologue, Dap1, while pound signs indicate key non-conserved residues. The sequences of the two proteins are shown below with the identical sequences shaded in gray. The positions of four residues are indicated as a reference point. PGRMC1 residues Asp120, Tyr107, Tyr113 and Tyr164 are required for heme binding in PGRMC1, and the residues that are analogous to Asp120 and Tyr164 are required for heme binding in Dap1.
Fig. 3
Fig. 3
A proposed model for PGRMC1 in progesterone signaling and metabolism. PGRMC1 is part of a progesterone binding complex in which it binds to an uncharacterized steroid/drug binding protein (S/D-BP) that also has affinity for corticosterone, testosterone, cortisol and haloperidol. Progesterone binding by this complex has anti-apoptotic activity that requires PGRMC1. Heme (H) is the ligand for PGRMC1, and heme binding is required for its anti-apoptotic function. Cyp21/21-hydroxylase also binds to PGRMC1 and metabolizes progesterone to 11-deoxycorticosterone.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ace CI, Okulicz WC. Microarray profiling of progesterone-regulated endometrial genes during the rhesus monkey secretory phase. Reprod Biol Endocrinol. 2004;2:54. - PMC - PubMed
    1. Albro PW, Corbett JT, Harris M, Lawson LD. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on lipid profiles in tissue of the Fischer rat. Chem Biol Interact. 1978;23:315–330. - PubMed
    1. Bard M, Lees ND, Burrows LS, Kleinhans FW. Differences in crystal violet uptake and cation-induced death among yeast sterol mutants. J Bacteriol. 1978;135:1146–1148. - PMC - PubMed
    1. Bramley TA, Menzies GS, Rae MT, Scobie G. Non-genomic steroid receptors in the bovine ovary. Domest Anim Endocrinol. 2002;23:3–12. - PubMed
    1. Bruno RD, Njar VC. Targeting cytochrome P450 enzymes: a new approach in anti-cancer drug development. Bioorg Med Chem. 2007;15:5047–5060. - PMC - PubMed

Publication types