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


METHODS
Comparative and laboratory study.


METHODS
University teaching hospital reproductive endocrinology and infertility practice.


METHODS
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.


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


METHODS
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.


RESULTS
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.


CONCLUSIONS
GHRH and SV1 may play a role in promoting the development of endometriosis.
Fu
Li
L
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Osuga
Yutaka
Y
Yano
Tetsu
T
Takemura
Yuri
Y
Morimoto
Chieko
C
Hirota
Yasushi
Y
Schally
Andrew V
AV
Taketani
Yuji
Y
D000328:Adult; D017398:Alternative Splicing; D001854:Bone Marrow Cells / Q000473:pathology; D017931:DNA Primers; D004715:Endometriosis / Q000235:genetics* / Q000601:surgery; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics; D006801:Humans; D010535:Laparoscopy; D017493:Leukocyte Common Antigens; D008597:Menstrual Cycle / Q000502:physiology; D010053:Ovary / Q000503:physiopathology; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology
D017931:DNA Primers; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013007:Growth Hormone-Releasing Hormone; D017493:Leukocyte Common Antigens; C048250:somatotropin releasing hormone receptor