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PMID: 21406445 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Expression pattern of endothelin system components and localization of smooth muscle cells in the human pre-ovulatory follicle.

Human reproduction (Oxford, England) ·Vol. 26 ·No. 5 ·2011-05-00 ·Pages 1171-80

Choi DH, Kim EK, Kim KH, Lee KA, Kang DW, Kim HY, Bridges P, Ko C

Abstract

Whether ovarian follicular rupture involves contractile activity or not has been debated for decades. Recently, study in the rodents has indicated that an endogenously produced potent vasoconstrictive peptide, endothelin-2 (EDN2), may induce follicular constriction immediately prior to ovulation. This study was aimed to systematically characterize the human ovarian endothelin system and localize smooth muscle cells to assess the possible involvement of contractile activity in human ovulation. This is a prospective experimental study. Study subjects were 20 women aged 20-38 years who underwent IVF owing to tubal or male factors. Expression patterns of messenger RNAs (mRNAs) for EDN1, EDN2, EDN3, endothelin-converting enzyme-1 (ECE1 and ECE2), endothelin receptor A (ET(A)) and ET(B) in the granulosa cells (GCs) and cumulus cells and endothelin peptide concentration in the pre-ovulatory follicles were measured at 36 h after hCG injection. In addition, localization of ovarian smooth muscle cells and endothelin receptor expression were determined in normal (non-IVF patient) ovaries. Pre-ovulatory follicles express mRNA for EDN1 and EDN2, ECE1, ECE2, ET(A) and ET(B), but not EDN3, contain highly concentrated endothelin peptides (105.9 pg/ml) and are surrounded by theca externa that are made mostly of multicell layer non-vascular smooth muscle cells. ET(A) expression is localized in the smooth muscle cells of theca externa, theca interna and GC, whereas ET(B) expression is confined to theca interna. Pre-ovulatory follicles contain highly concentrated endothelins and are surrounded by non-vascular smooth muscle cells that express endothelin receptor, suggesting involvement of endothelin-induced contractile action in ovulation in the human ovary.

MeSH Terms
Adult Aspartic Acid Endopeptidases/analysis,genetics,metabolism Cumulus Cells/metabolism Endothelin-Converting Enzymes Endothelins/analysis,genetics,metabolism Female Fertilization in Vitro Follicular Fluid/metabolism Granulosa Cells/metabolism Humans Metalloendopeptidases/analysis,genetics,metabolism Myocytes, Smooth Muscle/cytology Ovarian Follicle/cytology,metabolism Ovulation RNA, Messenger/metabolism Receptors, Endothelin/analysis,genetics,metabolism
Chemicals
Endothelins RNA, Messenger Receptors, Endothelin Aspartic Acid Endopeptidases Metalloendopeptidases ECE1 protein, human ECE2 protein, human Endothelin-Converting Enzymes
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Choi Dong-Hee
Department of Obstetrics and Gynaecology, CHA University, Bundang-Si, Kyounggi-do, Republic of Korea.
Kim Eun Kyung
Kim Kyeoung-Hwa
Lee Kyung-Ah
Kang Dong-Wook
Kim Hey Young
Bridges Phillip
Ko Chemyong
References (53)
53 references, click to expand
  1. Endothelin receptor antagonists: structures, synthesis, selectivity and therapeutic applications.
    Curr Med Chem. 2002 Feb;9(3):349-83 PMID: 11860362
  2. Potential role of nitric oxide in endothelin-1 provoked inhibition of progesterone secretion by isolated ovarian granulosa cells.
    Endocr Regul. 2002 Mar;36(1):19-22 PMID: 11971747
  3. The role of endothelin-1 in regulating human granulosa cell proliferation and steroidogenesis in vitro.
    J Clin Endocrinol Metab. 1995 Dec;80(12):3708-14 PMID: 8530623
  4. Endothelin: 20 years from discovery to therapy.
    Can J Physiol Pharmacol. 2008 Aug;86(8):485-98 PMID: 18758495
  5. Paracrine regulation of the resumption of oocyte meiosis by endothelin-1.
    Dev Biol. 2009 Mar 1;327(1):62-70 PMID: 19111534
  6. A prospective randomized comparison of luteal phase versus concurrent follicular phase initiation of gonadotropin-releasing hormone agonist for in vitro fertilization.
    Fertil Steril. 1992 Oct;58(4):744-9 PMID: 1426320
  7. An ultrastructural study of smooth muscle-like cells in the theca externa of ovarian follicles in the rat.
    Anat Rec. 1970 Jun;167(2):127-31 PMID: 5445022
  8. A novel pathway involving progesterone receptor, endothelin-2, and endothelin receptor B controls ovulation in mice.
    Mol Endocrinol. 2006 Nov;20(11):2784-95 PMID: 16887885
  9. Intrafollicular pressure decreases in hamster preovulatory follicles during smooth muscle cell contraction in vitro.
    J Exp Zool. 1982 Dec 30;224(3):417-26 PMID: 7153733
  10. MEASUREMENTS OF INTRAFOLLICULAR PRESSURES IN THE RABBIT OVARY.
    Am J Physiol. 1963 Dec;205:1067-72 PMID: 14084958
  11. In vitro ovulation of hamster oocytes depends on contraction of follicular smooth muscle cells.
    J Exp Zool. 1982 Dec 30;224(3):409-15 PMID: 7153732
  12. Endothelin (ET)-1 and ET-3 inhibit estrogen and cAMP production by rat granulosa cells in vitro.
    J Endocrinol. 1998 May;157(2):209-15 PMID: 9659283
  13. Primer3 on the WWW for general users and for biologist programmers.
    Methods Mol Biol. 2000;132:365-86 PMID: 10547847
  14. Role of hypoxia in the regulation of periovulatory EDN2 expression in the mouse.
    Can J Physiol Pharmacol. 2008 Jun;86(6):310-9 PMID: 18516093
  15. Cellular distribution of endothelin-converting enzyme-1 in human tissues.
    J Histochem Cytochem. 1999 Apr;47(4):447-62 PMID: 10082746
  16. Ovulation: new dimensions and new regulators of the inflammatory-like response.
    Annu Rev Physiol. 2002;64:69-92 PMID: 11826264
  17. Identification, characterization, and biological activity of endothelin receptors in human ovary.
    J Clin Endocrinol Metab. 1997 Dec;82(12):4122-9 PMID: 9398725
  18. Ovarian contractility and its relationship to ovulation: a review.
    Biol Reprod. 1978 Oct;19(3):540-51 PMID: 31208
  19. Smooth muscle alpha actin and myosin heavy chain expression in the vascular smooth muscle cells surrounding human endometrial arterioles.
    Hum Reprod. 1999 Dec;14(12):3095-100 PMID: 10601102
  20. Historical review: Endothelin.
    Trends Pharmacol Sci. 2004 Apr;25(4):219-24 PMID: 15063086
  21. Expression of endothelin-1 gene and protein in human granulosa cells.
    J Clin Endocrinol Metab. 1996 Apr;81(4):1428-33 PMID: 8636346
  22. GnRH antagonist, cetrorelix, for pituitary suppression in modern, patient-friendly assisted reproductive technology.
    Expert Opin Drug Metab Toxicol. 2009 Oct;5(10):1323-36 PMID: 19761413
  23. Hirschsprung's disease: genetic and functional associations of Down's and Waardenburg syndromes.
    Semin Pediatr Surg. 1998 Aug;7(3):156-61 PMID: 9718653
  24. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology.
    Pharmacol Rev. 1994 Sep;46(3):325-415 PMID: 7831383
  25. The role of follicular smooth muscle cells in hamster ovulation.
    J Exp Zool. 1981 Jun;216(3):469-82 PMID: 7276896
  26. Endothelin-2 induces oviductal contraction via endothelin receptor subtype A in rats.
    J Endocrinol. 2007 Jun;193(3):383-91 PMID: 17535876
  27. Immunoreactive endothelin-1, endothelin-2 and big endothelin-1 in follicular fluids of women undergoing ovulation induction for in-vitro fertilization.
    Hum Reprod. 1996 Feb;11(2):269-73 PMID: 8671207
  28. Endothelin in health and disease.
    Bosn J Basic Med Sci. 2004 Jul;4(3):31-4 PMID: 15629009
  29. Identification of a novel role for endothelins within the oviduct.
    Endocrinology. 2010 Jun;151(6):2858-67 PMID: 20357223
  30. Modulation of steroidogenesis in human ovarian granulosa cells during aging.
    Endocr Regul. 2000 Sep;34(3):157-60 PMID: 11074660
  31. High levels of immunoreactive endothelin-1 in human follicular fluids.
    Hum Reprod. 1993 May;8(5):674-7 PMID: 8314957
  32. Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study.
    Chest. 2003 Jul;124(1):247-54 PMID: 12853530
  33. Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide.
    Proc Natl Acad Sci U S A. 1988 Sep;85(18):6964-7 PMID: 3045827
  34. Modelling the structures of the isoforms of human endothelins based on the crystal structure of human endothelin-I.
    Biochem Soc Trans. 1994 Nov;22(4):1037-43 PMID: 7698403
  35. Endothelin-1: expression and role in human corpus luteum.
    Am J Reprod Immunol. 1998 Nov;40(5):370-6 PMID: 9870082
  36. Localization of actin and myosin in the rat oocyte and follicular wall by immunofluorescence.
    Anat Rec. 1977 Mar;187(3):311-28 PMID: 322543
  37. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle.
    Endocr Rev. 2003 Aug;24(4):428-65 PMID: 12920150
  38. FOLLICULAR PRESSURE AND DISTENSIBILITY IN OVULATION.
    Am J Physiol. 1964 Sep;207:590-4 PMID: 14220028
  39. The endothelin system in human and monkey ovaries: in situ gene expression of the different components.
    Cell Tissue Res. 1999 Jan;295(1):101-9 PMID: 10048935
  40. The single or dual administration of the gonadotropin-releasing hormone antagonist Cetrorelix in an in vitro fertilization-embryo transfer program.
    Fertil Steril. 1994 Sep;62(3):468-76 PMID: 8062940
  41. A novel potent vasoconstrictor peptide produced by vascular endothelial cells.
    Nature. 1988 Mar 31;332(6163):411-5 PMID: 2451132
  42. Endothelin receptor antagonists in pulmonary arterial hypertension.
    J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):62S-67S PMID: 15194180
  43. Production and binding of endothelin-2 (EDN2) in the rat ovary: endothelin receptor subtype A (EDNRA)-mediated contraction.
    Reprod Fertil Dev. 2010;22(5):780-7 PMID: 20450830
  44. Rat ovarian granulosa cell as a site of endothelin reception and action: attenuation of gonadotropin-stimulated steroidogenesis via perturbation of the A-kinase signaling pathway.
    Biol Reprod. 1994 Nov;51(5):1058-65 PMID: 7849183
  45. Endothelin-2 in ovarian follicle rupture.
    Endocrinology. 2006 Apr;147(4):1770-9 PMID: 16410304
  46. Immunoreactive endothelins in human follicular fluid.
    Gynecol Obstet Invest. 1993;36(1):12-4 PMID: 8349171
  47. Correlation between 21 amino acid endothelin, intrafollicular steroids and follicle size in stimulated cycles.
    Hum Reprod. 1999 Sep;14(9):2323-7 PMID: 10469703
  48. Simplification of the method of in vitro fertilization: sonographic measurements of follicular diameter as the sole index of follicular maturity.
    J In Vitro Fert Embryo Transf. 1985 Mar;2(1):17-22 PMID: 3926921
  49. Effects of genistein on the periovulatory expression of messenger ribonucleic acid for matrix metalloproteinases and tissue inhibitors of metalloproteinases in the rat ovary.
    Reproduction. 2001 Feb;121(2):259-65 PMID: 11226050
  50. Drugs that block smooth muscle contraction inhibit in vivo ovulation in hamsters.
    J Exp Zool. 1981 Jun;216(3):483-91 PMID: 7196941
  51. The ovarian endothelin network: an evolving story.
    Trends Endocrinol Metab. 2007 Dec;18(10):379-85 PMID: 17997104
  52. Effects of follicle-stimulating hormone on endothelin receptors in cultured rat ovarian granulosa cells.
    J Cardiovasc Pharmacol. 1998;31 Suppl 1:S225-9 PMID: 9595444
  53. Vascular endothelin-B receptor system in vivo plays a favorable inhibitory role in vascular remodeling after injury revealed by endothelin-B receptor-knockout mice.
    Circulation. 2002 Oct 8;106(15):1991-8 PMID: 12370225
Article Info
Journal
Human reproduction (Oxford, England)
Abbr.
Hum Reprod
ISSN
1460-2350
DOI
10.1093/humrep/der066
Published
2011-05-00
Epub
2011-00-15
Pages
1171-80
Language
English
Region
England
NLM ID
8701199
PMCID
PMC3079471
Subset
IM
Grants
NICHD NIH HHS · R01HD052694 · United States
External Links
PubMed source DOI: 10.1093/humrep/der066 PMC Full Text View journal details
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