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

Abstract

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. Comparative and laboratory study. University teaching hospital reproductive endocrinology and infertility practice. 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. Ectopic endometrial stromal cells (ESC) were isolated and cultured with or without GHRH. 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. 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. GHRH and SV1 may play a role in promoting the development of endometriosis.