PGRMC1 and Premature Menopause

The association between PGRMC1 and premature menopause is supported by several lines of genetic evidence. A familial study identified a mother and daughter with premature ovarian failure carrying mutations in PGRMC1, and additional case series have reported missense variants, including c.556C>T (p.Pro186Ser), in patients with the disorder (PMID:18782852). However, conflicting evidence exists, as one study in a Han Chinese cohort found a similar variant with predicted benign impact (PMID:25246111). Overall, the genetic data are limited by small numbers of independent probands and some inconsistency across studies.

Functional assessment studies bolster the genetic findings by demonstrating that PGRMC1 plays a critical role in mediating progesterone’s antiapoptotic action in ovarian cells (PMID:17991724). The protein product of PGRMC1 is implicated in key pathways regulating follicle survival and steroid hormone biosynthesis, and perturbation of its function may lead to increased apoptosis and diminished ovarian reserve. Although the functional assays provide moderate support by correlating altered PGRMC1 activity with the cellular phenotype observed in premature ovarian failure, the overall evidence remains limited. Key take‑home: Despite some promising functional data, the clinical association of PGRMC1 with premature menopause requires further corroboration by additional, larger-scale studies.

References

• Human molecular genetics • 2008 • Alterations in the expression, structure and function of progesterone receptor membrane component-1 in premature ovarian failure PMID:18782852
• Reproductive biomedicine online • 2014 • Analysis of progesterone receptor membrane component 1 mutation in Han Chinese women with premature ovarian failure PMID:25246111
• Endocrinology • 2008 • Progesterone receptor membrane component-1 mediates progesterone's antiapoptotic action in granulosa cells PMID:17991724

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