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Published in: Reproductive Biology and Endocrinology 1/2010

Open Access 01-12-2010 | Research

Down-regulation of progesterone receptor membrane component 1 (PGRMC1) in peripheral nucleated blood cells associated with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS)

Authors: Jens Schuster, Teresia Karlsson, Per-Olof Karlström, Inger Sundström Poromaa, Niklas Dahl

Published in: Reproductive Biology and Endocrinology | Issue 1/2010

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Abstract

Background

Progesterone receptor membrane component 1 (PGRMC1) is a member of a progesterone-binding complex implicated in female reproduction. We aimed i) to determine the natural expression of PGRMC1 in peripheral nucleated blood cells throughout the menstrual cycle and ii) to investigate any association between PGRMC1 levels in leukocytes and conditions characterized by reduced fertility.

Methods

We analyzed PGRMC1 expression in peripheral leukocytes from 15 healthy cycling women over four weeks. Additionally, we determined PGRMC1 levels in samples from patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) as well as in healthy postmenopausal women and male controls. The levels of PGRMC1 protein in nucleated peripheral blood cells were quantified by Western blot analysis.

Results

PGRMC1 levels did not vary significantly throughout the menstrual cycle. We observed a significant down-regulation of PGRMC1 in postmenopausal women and in patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) when compared to early follicular phase of healthy women.

Conclusion

This study suggests that reduced levels of PGRMC1 in peripheral leukocytes are associated with perturbed ovulatory function.
Appendix
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Literature
1.
go back to reference Peluso JJ: Non-genomic actions of progesterone in the normal and neoplastic mammalian ovary. Semin Reprod Med. 2007, 25: 198-207. 10.1055/s-2007-973432.CrossRefPubMed Peluso JJ: Non-genomic actions of progesterone in the normal and neoplastic mammalian ovary. Semin Reprod Med. 2007, 25: 198-207. 10.1055/s-2007-973432.CrossRefPubMed
2.
go back to reference Losel RM, Besong D, Peluso JJ, Wehling M: Progesterone receptor membrane component 1--many tasks for a versatile protein. Steroids. 2008, 73: 929-934. 10.1016/j.steroids.2007.12.017.CrossRefPubMed Losel RM, Besong D, Peluso JJ, Wehling M: Progesterone receptor membrane component 1--many tasks for a versatile protein. Steroids. 2008, 73: 929-934. 10.1016/j.steroids.2007.12.017.CrossRefPubMed
3.
go back to reference Peluso JJ, Romak J, Liu X: Progesterone receptor membrane component-1 (PGRMC1) is the mediator of progesterone's antiapoptotic action in spontaneously immortalized granulosa cells as revealed by PGRMC1 small interfering ribonucleic acid treatment and functional analysis of PGRMC1 mutations. Endocrinology. 2008, 149: 534-543. 10.1210/en.2007-1050.PubMedCentralCrossRefPubMed Peluso JJ, Romak J, Liu X: Progesterone receptor membrane component-1 (PGRMC1) is the mediator of progesterone's antiapoptotic action in spontaneously immortalized granulosa cells as revealed by PGRMC1 small interfering ribonucleic acid treatment and functional analysis of PGRMC1 mutations. Endocrinology. 2008, 149: 534-543. 10.1210/en.2007-1050.PubMedCentralCrossRefPubMed
4.
go back to reference Gerdes D, Wehling M, Leube B, Falkenstein E: Cloning and tissue expression of two putative steroid membrane receptors. Biol Chem. 1998, 379: 907-911. 10.1515/bchm.1998.379.7.907.PubMed Gerdes D, Wehling M, Leube B, Falkenstein E: Cloning and tissue expression of two putative steroid membrane receptors. Biol Chem. 1998, 379: 907-911. 10.1515/bchm.1998.379.7.907.PubMed
5.
go back to reference Mansouri MR, Schuster J, Badhai J, Stattin L, Losel R, Wehling M, Carlsson B, Hovatta O, Karlstrom PO, Golovleva I, Toniolo D, Bione S, Peluso J, Dahl N: Alterations in the expression, structure and function of progesterone receptor membrane component-1 (PGRMC1) in premature ovarian failure. Hum Mol Genet. 2008, 17: 3776-3783. 10.1093/hmg/ddn274.PubMedCentralCrossRefPubMed Mansouri MR, Schuster J, Badhai J, Stattin L, Losel R, Wehling M, Carlsson B, Hovatta O, Karlstrom PO, Golovleva I, Toniolo D, Bione S, Peluso J, Dahl N: Alterations in the expression, structure and function of progesterone receptor membrane component-1 (PGRMC1) in premature ovarian failure. Hum Mol Genet. 2008, 17: 3776-3783. 10.1093/hmg/ddn274.PubMedCentralCrossRefPubMed
6.
go back to reference Cahill MA: Progesterone receptor membrane component 1: an integrative review. J Steroid Biochem Mol Biol. 2007, 105: 16-36. 10.1016/j.jsbmb.2007.02.002.CrossRefPubMed Cahill MA: Progesterone receptor membrane component 1: an integrative review. J Steroid Biochem Mol Biol. 2007, 105: 16-36. 10.1016/j.jsbmb.2007.02.002.CrossRefPubMed
7.
go back to reference Engmann L, Losel R, Wehling M, Peluso JJ: Progesterone regulation of human granulosa/luteal cell viability by an RU486-independent mechanism. J Clin Endocrinol Metab. 2006, 91: 4962-4968. 10.1210/jc.2006-1128.CrossRefPubMed Engmann L, Losel R, Wehling M, Peluso JJ: Progesterone regulation of human granulosa/luteal cell viability by an RU486-independent mechanism. J Clin Endocrinol Metab. 2006, 91: 4962-4968. 10.1210/jc.2006-1128.CrossRefPubMed
8.
go back to reference Peluso JJ, Pappalardo A, Losel R, Wehling M: Progesterone membrane receptor component 1 expression in the immature rat ovary and its role in mediating progesterone's antiapoptotic action. Endocrinology. 2006, 147: 3133-3140. 10.1210/en.2006-0114.CrossRefPubMed Peluso JJ, Pappalardo A, Losel R, Wehling M: Progesterone membrane receptor component 1 expression in the immature rat ovary and its role in mediating progesterone's antiapoptotic action. Endocrinology. 2006, 147: 3133-3140. 10.1210/en.2006-0114.CrossRefPubMed
9.
go back to reference Rohe HJ, Ahmed IS, Twist KE, Craven RJ: PGRMC1 (progesterone receptor membrane component 1): A targetable protein with multiple functions in steroid signaling, P450 activation and drug binding. Pharmacol Ther. 2009, 121: 14-19. 10.1016/j.pharmthera.2008.09.006.PubMedCentralCrossRefPubMed Rohe HJ, Ahmed IS, Twist KE, Craven RJ: PGRMC1 (progesterone receptor membrane component 1): A targetable protein with multiple functions in steroid signaling, P450 activation and drug binding. Pharmacol Ther. 2009, 121: 14-19. 10.1016/j.pharmthera.2008.09.006.PubMedCentralCrossRefPubMed
10.
go back to reference Hughes AL, Powell DW, Bard M, Eckstein J, Barbuch R, Link AJ, Espenshade PJ: Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. Cell Metab. 2007, 5: 143-149. 10.1016/j.cmet.2006.12.009.CrossRefPubMed Hughes AL, Powell DW, Bard M, Eckstein J, Barbuch R, Link AJ, Espenshade PJ: Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. Cell Metab. 2007, 5: 143-149. 10.1016/j.cmet.2006.12.009.CrossRefPubMed
11.
go back to reference Zhang L, Kanda Y, Roberts DJ, Ecker JL, Losel R, Wehling M, Peluso JJ, Pru JK: Expression of progesterone receptor membrane component 1 and its partner serpine 1 mRNA binding protein in uterine and placental tissues of the mouse and human. Mol Cell Endocrinol. 2008, 287: 81-89. 10.1016/j.mce.2008.02.012.CrossRefPubMed Zhang L, Kanda Y, Roberts DJ, Ecker JL, Losel R, Wehling M, Peluso JJ, Pru JK: Expression of progesterone receptor membrane component 1 and its partner serpine 1 mRNA binding protein in uterine and placental tissues of the mouse and human. Mol Cell Endocrinol. 2008, 287: 81-89. 10.1016/j.mce.2008.02.012.CrossRefPubMed
12.
go back to reference T.R.E.A.-s.P.c.-workshop: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004, 19: 41-47. 10.1093/humrep/deh098.CrossRef T.R.E.A.-s.P.c.-workshop: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004, 19: 41-47. 10.1093/humrep/deh098.CrossRef
13.
go back to reference Peluso JJ, Liu X, Saunders MM, Claffey KP, Phoenix K: Regulation of ovarian cancer cell viability and sensitivity to cisplatin by progesterone receptor membrane component-1. J Clin Endocrinol Metab. 2008, 93: 1592-1599. 10.1210/jc.2007-2771.CrossRefPubMed Peluso JJ, Liu X, Saunders MM, Claffey KP, Phoenix K: Regulation of ovarian cancer cell viability and sensitivity to cisplatin by progesterone receptor membrane component-1. J Clin Endocrinol Metab. 2008, 93: 1592-1599. 10.1210/jc.2007-2771.CrossRefPubMed
14.
go back to reference Peluso JJ, Liu X, Gawkowska A, Johnston-Macananny E: Progesterone Activates a Progesterone Receptor Membrane Component 1-dependent Mechanism That Promotes Human Granulosa/luteal Cell Survival But Not Progesterone Secretion. J Clin Endocrinol Metab. 2009 Peluso JJ, Liu X, Gawkowska A, Johnston-Macananny E: Progesterone Activates a Progesterone Receptor Membrane Component 1-dependent Mechanism That Promotes Human Granulosa/luteal Cell Survival But Not Progesterone Secretion. J Clin Endocrinol Metab. 2009
15.
go back to reference Nilsson EE, Stanfield J, Skinner MK: Interactions between progesterone and tumor necrosis factor-alpha in the regulation of primordial follicle assembly. Reproduction. 2006, 132: 877-886. 10.1530/REP-06-0045.CrossRefPubMed Nilsson EE, Stanfield J, Skinner MK: Interactions between progesterone and tumor necrosis factor-alpha in the regulation of primordial follicle assembly. Reproduction. 2006, 132: 877-886. 10.1530/REP-06-0045.CrossRefPubMed
16.
go back to reference Krebs CJ, Jarvis ED, Chan J, Lydon JP, Ogawa S, Pfaff DW: A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors. Proc Natl Acad Sci USA. 2000, 97: 12816-12821. 10.1073/pnas.97.23.12816.PubMedCentralCrossRefPubMed Krebs CJ, Jarvis ED, Chan J, Lydon JP, Ogawa S, Pfaff DW: A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors. Proc Natl Acad Sci USA. 2000, 97: 12816-12821. 10.1073/pnas.97.23.12816.PubMedCentralCrossRefPubMed
17.
go back to reference Neubauer H, Clare SE, Wozny W, Schwall GP, Poznanovic S, Stegmann W, Vogel U, Sotlar K, Wallwiener D, Kurek R, Fehm T, Cahill MA: Breast cancer proteomics reveals correlation between estrogen receptor status and differential phosphorylation of PGRMC1. Breast Cancer Res. 2008, 10: R85-10.1186/bcr2155.PubMedCentralCrossRefPubMed Neubauer H, Clare SE, Wozny W, Schwall GP, Poznanovic S, Stegmann W, Vogel U, Sotlar K, Wallwiener D, Kurek R, Fehm T, Cahill MA: Breast cancer proteomics reveals correlation between estrogen receptor status and differential phosphorylation of PGRMC1. Breast Cancer Res. 2008, 10: R85-10.1186/bcr2155.PubMedCentralCrossRefPubMed
18.
go back to reference Roell A, Schueller P, Schultz A, Losel R, Wehling M, Christ M, Feuring M: Effect of oral contraceptives and ovarian cycle on platelet function. Platelets. 2007, 18: 165-170. 10.1080/09537100600936224.CrossRefPubMed Roell A, Schueller P, Schultz A, Losel R, Wehling M, Christ M, Feuring M: Effect of oral contraceptives and ovarian cycle on platelet function. Platelets. 2007, 18: 165-170. 10.1080/09537100600936224.CrossRefPubMed
19.
go back to reference Goldstein J, Cushman M, Badger GJ, Johnson JV: Effect of depomedroxyprogesterone acetate on coagulation parameter: a pilot study. Fertil Steril. 2007, 87: 1267-1270. 10.1016/j.fertnstert.2006.11.040.CrossRefPubMed Goldstein J, Cushman M, Badger GJ, Johnson JV: Effect of depomedroxyprogesterone acetate on coagulation parameter: a pilot study. Fertil Steril. 2007, 87: 1267-1270. 10.1016/j.fertnstert.2006.11.040.CrossRefPubMed
20.
go back to reference Medina RA, Aranda E, Verdugo C, Kato S, Owen GI: The action of ovarian hormones in cardiovascular disease. Biol Res. 2003, 36: 325-341. 10.4067/S0716-97602003000300005.CrossRefPubMed Medina RA, Aranda E, Verdugo C, Kato S, Owen GI: The action of ovarian hormones in cardiovascular disease. Biol Res. 2003, 36: 325-341. 10.4067/S0716-97602003000300005.CrossRefPubMed
Metadata
Title
Down-regulation of progesterone receptor membrane component 1 (PGRMC1) in peripheral nucleated blood cells associated with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS)
Authors
Jens Schuster
Teresia Karlsson
Per-Olof Karlström
Inger Sundström Poromaa
Niklas Dahl
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2010
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-8-58

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