Pgrmc2, or progesterone receptor membrane component 2, is a heme-binding protein. It serves as an intracellular haem chaperone, crucial for delivering labile, or signalling haem, to the nucleus [1]. This function is significant as haem is an essential prosthetic group for numerous proteins and a key signalling molecule in many physiological processes. Pgrmc2 is also potentially involved in progesterone signalling, cytochrome P450 binding, and may regulate cytochrome P450 enzyme activity [4].

In adipose-specific Pgrmc2-null mice, deletion of Pgrmc2 in brown fat led to reduced labile haem in the nucleus, increased stability of haem-responsive transcriptional repressors, mitochondrial defects, and impaired adaptive thermogenesis, making them more prone to metabolic deterioration on a high-fat diet [1]. In zebrafish, pgrmc2 -/- mutants showed subfertility due to reduced oocyte maturation, likely via regulation of receptors and steroids in the ovary [2]. Heart-specific knockout (KO) mice (MyH6•Pgrmc2flox/flox) revealed that Pgrmc2 is a mediator of steroid hormones for rapid calcium signalling in cardiomyocytes, regulating the cardiac pressure-volume relationship. Under hypoxic conditions, KO hearts developed congestive left and right ventricular failure [3].

In conclusion, Pgrmc2 plays essential roles in adipocyte function, female fertility, and cardiac responses to stress as revealed through gene knockout models. These findings in mouse and zebrafish models contribute to understanding its role in metabolic diseases, female reproductive disorders, and heart diseases [1,2,3].

References:

1. Galmozzi, Andrea, Kok, Bernard P, Kim, Arthur S, Cravatt, Benjamin F, Saez, Enrique. 2019. PGRMC2 is an intracellular haem chaperone critical for adipocyte function. In Nature, 576, 138-142. doi:10.1038/s41586-019-1774-2. https://pubmed.ncbi.nlm.nih.gov/31748741/

2. Wu, Xin-Jun, Williams, Marcus Jermaul, Patel, Pujan Rameshkumar, Kew, Kimberly Ann, Zhu, Yong. 2019. Subfertility and reduced progestin synthesis in Pgrmc2 knockout zebrafish. In General and comparative endocrinology, 282, 113218. doi:10.1016/j.ygcen.2019.113218. https://pubmed.ncbi.nlm.nih.gov/31301284/

3. Amirrad, Farideh, La, Vivian, Ohadi, Sharareh, Mohieldin, Ashraf M, Nauli, Surya M. 2025. PGRMC2 is a pressure-volume regulator critical for myocardial responses to stress in mice. In Nature communications, 16, 2422. doi:10.1038/s41467-025-57707-8. https://pubmed.ncbi.nlm.nih.gov/40069180/

4. Wendler, Alexandra, Wehling, Martin. 2012. PGRMC2, a yet uncharacterized protein with potential as tumor suppressor, migration inhibitor, and regulator of cytochrome P450 enzyme activity. In Steroids, 78, 555-8. doi:10.1016/j.steroids.2012.12.002. https://pubmed.ncbi.nlm.nih.gov/23276631/