Skip to main content
Top
Published in: Reproductive Biology and Endocrinology 1/2012

Open Access 01-12-2012 | Research

Human prolyl hydroxylase expression in uterine leiomyoma during the menstrual cycle

Authors: Masaaki Iwahashi, Yasuteru Muragaki, Kazuhiko Ino

Published in: Reproductive Biology and Endocrinology | Issue 1/2012

Login to get access

Abstract

Background

To investigate the role of prolyl hydroxylase (PH), a key enzyme of collagen synthesis, in human uterine leiomyoma, PH expression was determined in the normal uterine myometrium and the leiomyoma tissues during the menstrual cycle.

Methods

The tissues were obtained from 40 regularly cycling women (aged 29 to 53 yr) who were undergoing abdominal hysterectomy for symptomatic uterine leiomyoma. Immunohistochemistry for human PH with specific monoclonal antibody was used for analysis.

Results

Immunohistochemical staining for PH revealed intense staining of leiomyoma cells in the uterine leiomyoma throughout the menstrual cycle, as compared with the adjacent normal myometrium. In the secretory phase, weak or no immunostaining for PH was detected in the normal myometrial tissues.

Conclusions

These results suggest that increased expression of PH might play an role in the physiology of uterine leiomyoma during the menstrual cycle.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lin CQ, Bissell MJ: Multi-faceted regulation of cell differentiation by extracellular matrix. FASEB J. 1993, 7: 737-743.PubMed Lin CQ, Bissell MJ: Multi-faceted regulation of cell differentiation by extracellular matrix. FASEB J. 1993, 7: 737-743.PubMed
2.
go back to reference Madri JA, Basson MD: Extracellular matrix-cell interactions: dynamic modulators of cell, tissue and organism structure and function. Lab Invest. 1992, 66: 519-521.PubMed Madri JA, Basson MD: Extracellular matrix-cell interactions: dynamic modulators of cell, tissue and organism structure and function. Lab Invest. 1992, 66: 519-521.PubMed
3.
go back to reference Haralson MA: Extracellular matrix and growth factors: an integrated interplay controlling tissue repair and progression to disease. Lab Invest. 1993, 69: 369-372.PubMed Haralson MA: Extracellular matrix and growth factors: an integrated interplay controlling tissue repair and progression to disease. Lab Invest. 1993, 69: 369-372.PubMed
4.
go back to reference Ferency A, Richart RM, Okazaki T: A comparative ultrastructural study of leiomyosarcoma, cellular leiomyoma, and leiomyoma of the uterus. Cancer. 1971, 28: 1004-1018. 10.1002/1097-0142(1971)28:4<1004::AID-CNCR2820280426>3.0.CO;2-M.CrossRef Ferency A, Richart RM, Okazaki T: A comparative ultrastructural study of leiomyosarcoma, cellular leiomyoma, and leiomyoma of the uterus. Cancer. 1971, 28: 1004-1018. 10.1002/1097-0142(1971)28:4<1004::AID-CNCR2820280426>3.0.CO;2-M.CrossRef
5.
go back to reference Srewart AE, Friedman AJ, Peck K, Nowak RA: Relative overexpression of collagen type I and collagen III messenger ribonucleic acids by uterine leiomyoma during the proliferative phase of the menstrual cycle. J Clin Endocrinol Metab. 1994, 79: 900-906. 10.1210/jc.79.3.900. Srewart AE, Friedman AJ, Peck K, Nowak RA: Relative overexpression of collagen type I and collagen III messenger ribonucleic acids by uterine leiomyoma during the proliferative phase of the menstrual cycle. J Clin Endocrinol Metab. 1994, 79: 900-906. 10.1210/jc.79.3.900.
6.
go back to reference Catherino WH, Leppert PC, Stenmark MH, Payson M, Potiog-Nahari C, Nieman LK, Segars JH: Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids. Gene Chromosome Canc. 2004, 40: 204-217. 10.1002/gcc.20035.CrossRef Catherino WH, Leppert PC, Stenmark MH, Payson M, Potiog-Nahari C, Nieman LK, Segars JH: Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids. Gene Chromosome Canc. 2004, 40: 204-217. 10.1002/gcc.20035.CrossRef
7.
go back to reference Leppert PC, Baginski T, Prupas C, Catherino WH, Pletcher S, Segars JH: Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium. Fertil Steril. 2004, 82 (suppl3): 1182-1187.PubMedCentralCrossRefPubMed Leppert PC, Baginski T, Prupas C, Catherino WH, Pletcher S, Segars JH: Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium. Fertil Steril. 2004, 82 (suppl3): 1182-1187.PubMedCentralCrossRefPubMed
8.
go back to reference Myllyharju J, Kivirikko KI: Collagen, modifying enzymes and their mutations in humans, files and worms. Trends Genet. 2004, 20: 33-43. 10.1016/j.tig.2003.11.004.CrossRefPubMed Myllyharju J, Kivirikko KI: Collagen, modifying enzymes and their mutations in humans, files and worms. Trends Genet. 2004, 20: 33-43. 10.1016/j.tig.2003.11.004.CrossRefPubMed
9.
go back to reference Veit G, Kobbe B, Keene DR, Paulsson M, Koch M, Wagener R: Collagen XXVIII, a novel von Willebrand factor A domain-containing protein with many imperfections in the collagenous domain. J Biol Chem. 2006, 281: 3494-3504.CrossRefPubMed Veit G, Kobbe B, Keene DR, Paulsson M, Koch M, Wagener R: Collagen XXVIII, a novel von Willebrand factor A domain-containing protein with many imperfections in the collagenous domain. J Biol Chem. 2006, 281: 3494-3504.CrossRefPubMed
10.
go back to reference Myllyharju J: Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation of the response to hypoxia, and their roles as treatment targets. Ann Med. 2008, 40: 402-417. 10.1080/07853890801986594.CrossRefPubMed Myllyharju J: Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation of the response to hypoxia, and their roles as treatment targets. Ann Med. 2008, 40: 402-417. 10.1080/07853890801986594.CrossRefPubMed
11.
go back to reference Rhodes RE, Udenfriend S: Purification and properties of collagen proline hydroxylae from newborn rat skin. Arch Biochem Biophys. 1970, 139: 329-390. 10.1016/0003-9861(70)90485-6.CrossRef Rhodes RE, Udenfriend S: Purification and properties of collagen proline hydroxylae from newborn rat skin. Arch Biochem Biophys. 1970, 139: 329-390. 10.1016/0003-9861(70)90485-6.CrossRef
12.
go back to reference Cardinale GJ, Udenfriend S: Prolyl hydroxylase. Adv Enzymol. 1974, 41: 245-330.PubMed Cardinale GJ, Udenfriend S: Prolyl hydroxylase. Adv Enzymol. 1974, 41: 245-330.PubMed
13.
go back to reference Bai Y, Muragaki Y, Obata K, Iwata K, Ooshima A: Immunological properties of monoclonal antibodies to human and rat 4-prolyl hydroxylase. J Biochem. 1986, 99: 1563-1570.PubMed Bai Y, Muragaki Y, Obata K, Iwata K, Ooshima A: Immunological properties of monoclonal antibodies to human and rat 4-prolyl hydroxylase. J Biochem. 1986, 99: 1563-1570.PubMed
14.
go back to reference Ooshima A, Muragaki Y: Collagen metabolism in atherogenesis. Ann N Y Acad Sci. 1990, 598: 582-584. 10.1111/j.1749-6632.1990.tb42355.x.CrossRefPubMed Ooshima A, Muragaki Y: Collagen metabolism in atherogenesis. Ann N Y Acad Sci. 1990, 598: 582-584. 10.1111/j.1749-6632.1990.tb42355.x.CrossRefPubMed
15.
go back to reference Iwahashi M, Muragaki Y, Ikoma M, Mabuchi Y, Kobayashi A, Tanizaki Y, Ino K: Immuohistochemical analysis of collagen expression in uterine myomata during the menstrual cycle. Exp Ther Med. 2011, 2: 287-290.PubMedCentralPubMed Iwahashi M, Muragaki Y, Ikoma M, Mabuchi Y, Kobayashi A, Tanizaki Y, Ino K: Immuohistochemical analysis of collagen expression in uterine myomata during the menstrual cycle. Exp Ther Med. 2011, 2: 287-290.PubMedCentralPubMed
16.
go back to reference Iwahashi M, Muragaki Y: Increased type I and V collagen expression in uterine leiomyoma during the menstrual cycle. Fertil Steril. 2011, 95: 2137-2139. 10.1016/j.fertnstert.2010.12.028.CrossRefPubMed Iwahashi M, Muragaki Y: Increased type I and V collagen expression in uterine leiomyoma during the menstrual cycle. Fertil Steril. 2011, 95: 2137-2139. 10.1016/j.fertnstert.2010.12.028.CrossRefPubMed
17.
go back to reference Kivirikko KI, Myllyla R, Pihlajaniemi T: Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. FASEB J. 1989, 3: 1609-1617.PubMed Kivirikko KI, Myllyla R, Pihlajaniemi T: Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. FASEB J. 1989, 3: 1609-1617.PubMed
18.
go back to reference Edman JC, Ellis L, Blacher RW, Roth RA, Rutter WJ: Sequence of protein disulfide isomerase and implication of its relationship to thioredoxin. Nature. 1989, 317: 267-270.CrossRef Edman JC, Ellis L, Blacher RW, Roth RA, Rutter WJ: Sequence of protein disulfide isomerase and implication of its relationship to thioredoxin. Nature. 1989, 317: 267-270.CrossRef
19.
go back to reference Fong G-H, Takeda K: Role and regulation of prolyl hydroxylase domain proteins. Cell Death Differ. 2008, 10: 635-641.CrossRef Fong G-H, Takeda K: Role and regulation of prolyl hydroxylase domain proteins. Cell Death Differ. 2008, 10: 635-641.CrossRef
20.
go back to reference Rakesh KJ: A new target for tumor therapy. N Engl J Med. 2009, 360: 2669-2671. 10.1056/NEJMcibr0902054.CrossRef Rakesh KJ: A new target for tumor therapy. N Engl J Med. 2009, 360: 2669-2671. 10.1056/NEJMcibr0902054.CrossRef
21.
go back to reference Fraisl P, Aragones J, Carmeliet P: Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat Rev Drug Discov. 2009, 8: 139-152. 10.1038/nrd2761.CrossRefPubMed Fraisl P, Aragones J, Carmeliet P: Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat Rev Drug Discov. 2009, 8: 139-152. 10.1038/nrd2761.CrossRefPubMed
22.
go back to reference Semenza GL: Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis. Blood. 2009, 114: 2015-2019. 10.1182/blood-2009-05-189985.CrossRefPubMed Semenza GL: Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis. Blood. 2009, 114: 2015-2019. 10.1182/blood-2009-05-189985.CrossRefPubMed
23.
go back to reference Fong G-H: Regulation of angiogenesis by oxygen sensing mechanisms. J Mol Med. 2009, 87: 549-560. 10.1007/s00109-009-0458-z.CrossRefPubMed Fong G-H: Regulation of angiogenesis by oxygen sensing mechanisms. J Mol Med. 2009, 87: 549-560. 10.1007/s00109-009-0458-z.CrossRefPubMed
25.
go back to reference Aprelikova O, Pandolfi S, Tackett S, Ferreira M, Salnikow K, Ward Y, Lisinger JI, Barrett JC, Niederhuber J: Melanoma antigen-11 inhibits the hypoxia-inducible factor prolyl hydroxylase 2 and activates hypoxic response. Cancer Res. 2009, 69: 616-624. 10.1158/0008-5472.CAN-08-0811.PubMedCentralCrossRefPubMed Aprelikova O, Pandolfi S, Tackett S, Ferreira M, Salnikow K, Ward Y, Lisinger JI, Barrett JC, Niederhuber J: Melanoma antigen-11 inhibits the hypoxia-inducible factor prolyl hydroxylase 2 and activates hypoxic response. Cancer Res. 2009, 69: 616-624. 10.1158/0008-5472.CAN-08-0811.PubMedCentralCrossRefPubMed
26.
go back to reference Mayer A, Hoeckel M, Wree A, Leo C, Horn LC, Vaupel P: Lack of hypoxic response in uterine leiomyomas despite severe tissue hypoxia. Cancer Res. 2008, 68: 4719-4726. 10.1158/0008-5472.CAN-07-6339.CrossRefPubMed Mayer A, Hoeckel M, Wree A, Leo C, Horn LC, Vaupel P: Lack of hypoxic response in uterine leiomyomas despite severe tissue hypoxia. Cancer Res. 2008, 68: 4719-4726. 10.1158/0008-5472.CAN-07-6339.CrossRefPubMed
27.
go back to reference Mayer A, Hoeckel M, von Wallbrunn A, Horn LC, Wree A, Vaupel P: HIF-mediated hypoxic response is missing in severely hypoxic uterine leiomyomas. Adv Exp Med Biol. 2010, 662: 399-405. 10.1007/978-1-4419-1241-1_58.CrossRefPubMed Mayer A, Hoeckel M, von Wallbrunn A, Horn LC, Wree A, Vaupel P: HIF-mediated hypoxic response is missing in severely hypoxic uterine leiomyomas. Adv Exp Med Biol. 2010, 662: 399-405. 10.1007/978-1-4419-1241-1_58.CrossRefPubMed
Metadata
Title
Human prolyl hydroxylase expression in uterine leiomyoma during the menstrual cycle
Authors
Masaaki Iwahashi
Yasuteru Muragaki
Kazuhiko Ino
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2012
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-10-111

Other articles of this Issue 1/2012

Reproductive Biology and Endocrinology 1/2012 Go to the issue