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. 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.