Short Communication

Gerdes, Dirk; Wehling, Martin; Leube, B; Falkenstein, Elisabeth

doi:10.1515/bchm.1998.379.7.907

Cited by 96 publications

(22 citation statements)

References 80 publications

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“…In recent years, P4 is found to elicit a variety of fast, non-genomic effects on many physiological events, which are mediated by membrane P4 receptors, including PGRMC1 and PGRMC228 and mPRα, mPRβ as well mPRγ29. Missense mutations or reduced expression of PGRMC1 leads to premature ovarian failure (POF) in humans, which may be induced by the impaired binding of cytochrome P450 7A1 to PGRMC1213031.…”

Section: Discussionmentioning

confidence: 99%

Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis

Guo

Zhang

Wang

et al. 2016

Sci Rep

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Well-timed progression of primordial folliculogenesis is essential for mammalian female fertility. Progesterone (P4) inhibits primordial follicle formation under physiological conditions; however, P4 receptor that mediates this effect and its underlying mechanisms are unclear. In this study, we used an in vitro organ culture system to show that progesterone receptor membrane component 1 (PGRMC1) mediated P4-induced inhibition of oocyte meiotic prophase I and primordial follicle formation. We found that membrane-impermeable BSA-conjugated P4 inhibited primordial follicle formation similar to that by P4. Interestingly, PGRMC1 and its partner serpine1 mRNA-binding protein 1 were highly expressed in oocytes in perinatal ovaries. Inhibition or RNA interference of PGRMC1 abolished the suppressive effect of P4 on follicle formation. Furthermore, P4-PGRMC1 interaction blocked oocyte meiotic progression and decreased intra-oocyte cyclic AMP (cAMP) levels in perinatal ovaries. cAMP analog dibutyryl cAMP reversed P4–PGRMC1 interaction-induced inhibition of meiotic progression and follicle formation. Thus, our results indicated that PGRMC1 mediated P4-induced suppression of oocyte meiotic progression and primordial folliculogenesis by decreasing intra-oocyte cAMP levels.

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Section: Discussionmentioning

confidence: 99%

Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis

Guo

Zhang

Wang

et al. 2016

Sci Rep

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“…We confirmed that PGRMC1 protein levels were increased in patients with PCOS compared with the controls (S3 Fig and S4 Fig). PGRMC1, approximately 22 kDa, was first described in 1998 [32] as a putative progesterone-binding membrane receptor [33]. Also, PGRMC1 is expressed in human ovarian granulosa and luteal cells [34, 35], and its expression level and subcellular localization is regulated by gonadotropins [36].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling for Identification of Novel Biomarkers Differentially Expressed in Human Ovaries from Polycystic Ovary Syndrome Patients

Zhang

Deng

et al. 2016

PLoS ONE

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ObjectivesTo identify differential protein expression pattern associated with polycystic ovary syndrome (PCOS).MethodsTwenty women were recruited for the study, ten with PCOS as a test group and ten without PCOS as a control group. Differential in-gel electrophoresis (DIGE) analysis and mass spectroscopy were employed to identify proteins that were differentially expressed between the PCOS and normal ovaries. The differentially expressed proteins were further validated by western blot (WB) and immunohistochemistry (IHC).ResultsDIGE analysis revealed eighteen differentially expressed proteins in the PCOS ovaries of which thirteen were upregulated, and five downregulated. WB and IHC confirmed the differential expression of membrane-associated progesterone receptor component 1 (PGRMC1), retinol-binding protein 1 (RBP1), heat shock protein 90B1, calmodulin 1, annexin A6, and tropomyosin 2. Also, WB analysis revealed significantly (P<0.05) higher expression of PGRMC1 and RBP1 in PCOS ovaries as compared to the normal ovaries. The differential expression of the proteins was also validated by IHC.ConclusionsThe present study identified novel differentially expressed proteins in the ovarian tissues of women with PCOS that can serve as potential biomarkers for the diagnosis and development of novel therapeutics for the treatment of PCOS using molecular interventions.

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“…144 PGRMC1 also seems to play a role in the development of certain cancers, as recent reports suggest that it may be the inscrutable “sigma-2” receptor, a known biomarker of tumor cell proliferation. 145,146 In mammals, there exist two additional PGRMC1 family isoforms, PRGMC2/Dg6 147 and neudesin, 148 although it is not known if they also interact with CYP enzymes. PRGMC1 is highly expressed in the human liver and typically colocalized in the smooth endoplasmic reticulum (SER) with CYP proteins.…”

Section: Cytochrome P450 Interactions With Other Proteinsmentioning

confidence: 99%

Role of Protein–Protein Interactions in Cytochrome P450-Mediated Drug Metabolism and Toxicity

Kandel

Lampe

2014

Chem. Res. Toxicol.

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Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs) catalyze the elimination of most drugs and toxins from the human body. Protein–protein interactions play a critical role in this process. Historically, the study of CYP–protein interactions has focused on their electron transfer partners and allosteric mediators, cytochrome P450 reductase and cytochrome b5. However, CYPs can bind other proteins that also affect CYP function. Some examples include the progesterone receptor membrane component 1, damage resistance protein 1, human and bovine serum albumin, and intestinal fatty acid binding protein, in addition to other CYP isoforms. Furthermore, disruption of these interactions can lead to altered paths of metabolism and the production of toxic metabolites. In this review, we summarize the available evidence for CYP protein–protein interactions from the literature and offer a discussion of the potential impact of future studies aimed at characterizing noncanonical protein–protein interactions with CYP enzymes.

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Short Communication

Cited by 96 publications

References 80 publications

Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis

Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis

Proteomic Profiling for Identification of Novel Biomarkers Differentially Expressed in Human Ovaries from Polycystic Ovary Syndrome Patients

Role of Protein–Protein Interactions in Cytochrome P450-Mediated Drug Metabolism and Toxicity

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