Abstract
Progesterone (P4) is synthesized in the ovary and acts directly on granulosa cells of developing ovarian follicles to suppress their rate of mitosis and apoptosis. Granulosa cells do not express nuclear progesterone receptor (PGR) but rather progesterone receptor membrane component-1 (PGRMC1). PGRMC1 binds P4 and mediates P4's actions, as evidenced by PGRMC1 siRNA studies. PGRMC1 acts by binding plasminogen activator inhibitor 1 RNA-binding protein and regulating gene expression. Specifically, PGRMC1 suppresses some genes that promote cell death (i.e., Bad, Caspase-3, Caspase-4). P4 regulates gene expression in part by inhibiting PGRMC1 binding to Tcf/Lef transcription sites, thereby reducing Tcf/Lef transcriptional activity. Since Tcf/Lef transcription sites are located within the promoters of genes that initiate mitosis and/or apoptosis (i.e., c-jun and c-myc), P4-PGRMC1 mediated suppression of these Tcf/Lef regulated genes could account for P4's actions. PGRMC1 expression is also altered in women with polycystic ovarian syndrome, premature ovarian failure and infertility. Collectively, these observations support a role for PGRMC1 in regulating human ovarian follicle development.
Highlights
Progesterone receptor membrane component 1 (PGRMC1) plays a clinically important role in regulating ovarian function as demonstrated by the fact that PGRMC1 levels are reduced in some women with polycystic ovarian syndrome (Schuster et al, 2010) or premature ovarian failure (Mansouri et al, 2008; Schuster et al, 2010)
This mini review will focus on the experimental evidence that supports a role for P4-PGRMC1 signaling in regulating the granulosa cell functions of mitosis and apoptosis
While serum withdrawal has been a useful model system to demonstrate a functional role for P4-PGRMC1 signaling in regulating granulosa cell survival (Peluso et al, 2008, 2009), it is limited in that spontaneously immortalized granulosa cells (SIGCs) do not proliferate readily in serum-free www.frontiersin.org
Summary
Progesterone receptor membrane component 1 (PGRMC1) plays a clinically important role in regulating ovarian function as demonstrated by the fact that PGRMC1 levels are reduced in some women with polycystic ovarian syndrome (Schuster et al, 2010) or premature ovarian failure (Mansouri et al, 2008; Schuster et al, 2010). In addition to binding P4, PGRMC1 is an essential component in the mechanism through which P4 regulates granulosa cell function.
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