Expression and possible implication of growth hormone-releasing hormone receptor splice variant 1 in endometriosis

Fertil Steril. 2009 Jul;92(1):47-53. doi: 10.1016/j.fertnstert.2008.04.048. Epub 2008 Aug 5.

Abstract

Objective: To determine possible involvement of splice variant 1 (SV1), a variant of the pituitary growth hormone-releasing hormone (GHRH) receptor, in the development of endometriosis.

Design: Comparative and laboratory study.

Setting: University teaching hospital reproductive endocrinology and infertility practice.

Patient(s): Eutopic and ectopic endometrial tissues, and peritoneal bone marrow-derived cells were collected from women with or without endometriosis. Normal ovarian tissues were collected from women without endometriosis.

Intervention(s): Ectopic endometrial stromal cells (ESC) were isolated and cultured with or without GHRH.

Main outcome measure(s): Gene expression of GHRH and SV1 in the sample tissues was determined by reverse transcriptase (RT) nested polymerase chain reaction (PCR). Cyclic adenosine monophosphate (cAMP) production and 5-bromo-2'-deoxyuridine (BrdU) incorporation in ESC were measured using specific assay systems.

Result(s): We detected SV1 messenger RNA (mRNA) in 17 out of 27 (63%) ectopic endometrial tissues, which was statistically significantly higher than that detected in eutopic endometrial tissues (2 out of 47, 4%) and normal ovarian tissues (0 out of 14). A relatively low rate of GHRH mRNA was detected in ectopic endometrial tissues (6 out of 27, 24%) and in eutopic endometrial tissues (12 out of 47, 26%). In contrast, relatively high rates were detected in normal ovarian tissues (14 out of 14, 100%) and peritoneal bone marrow-derived cells (13 out of 16, 81%). We found that GHRH stimulated the production of cAMP and the incorporation of BrdU in SV1-expressing ESC.

Conclusion(s): GHRH and SV1 may play a role in promoting the development of endometriosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alternative Splicing*
  • Bone Marrow Cells / pathology
  • DNA Primers
  • Endometriosis / genetics*
  • Endometriosis / surgery
  • Female
  • Gene Expression Regulation
  • Genetic Variation*
  • Growth Hormone-Releasing Hormone / genetics
  • Humans
  • Laparoscopy
  • Leukocyte Common Antigens
  • Menstrual Cycle / physiology
  • Ovary / physiopathology
  • Receptors, Neuropeptide / genetics*
  • Receptors, Pituitary Hormone-Regulating Hormone / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / pathology
  • Stromal Cells / physiology

Substances

  • DNA Primers
  • Receptors, Neuropeptide
  • Receptors, Pituitary Hormone-Regulating Hormone
  • Growth Hormone-Releasing Hormone
  • Leukocyte Common Antigens
  • somatotropin releasing hormone receptor