Endometrial expression of relaxin and relaxin receptor in endometriosis

Abstract

Narrative AbstractOur studies demonstrate significantly lower expression of relaxin and its receptor in ectopic endometriotic tissues than their expression in eutopic endometrium and in endometrium from normal controls. These data suggest that in normal and eutopic endometrium, relaxin may exert a protective effect against endometriosis.The etiology of endometriosis, defined as the presence of endometrial stromal and glandular tissue growing at an extrauterine site, is poorly understood. The Sampson theory (1) does not sufficiently explain the etiology of this disease, since almost all women of reproductive age exhibit some degree of retrograde menstruation, but only 10-15% develop endometriosis (2). Additional factors must contribute to the development and progression of endometriosis.Relaxin is locally synthesized by human endometrium (3) and has potent effects in the endometrium, including decidualization (4). In human and rhesus monkey endometrium, relaxin is a powerful inhibitor of matrix metalloproteinases (MMPs) (3,5,6), which play an important role in the invasive process of endometriosis (7,8). Relaxin's action in target tissues is mediated by binding to its specific receptor, leucine-rich G protein-coupled receptor 7 (LGR7). Both relaxin and its LGR7 receptor are expressed in human endometrium (3,9,10) and human decidua (11,12).The current studies were performed to determine whether relaxin and/or its LGR7 receptor are expressed in human endometriotic tissues and whether their expression differ from that in endometrium from normal controls. We compared expression of relaxin mRNA and LGR7 mRNA in human endometriotic tissues to their expression in endometrium from normal controls. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Of the 40 patients, 21 were diagnosed with ovarian endometriosis on the basis of surgical pathology. These patients were classified by laparoscopy as having stage III (n = 18) or IV (n = 3) endometriosis using the revised American Society for Reproductive Medicine classification of endometriosis (15). Patients with laparoscopic evidence and histological confirmation of extra-ovarian endometriosis were not included in the study. Of the 21 endometriosis patients, 7 had only an endometrial biopsy available (eutopic endometrium), 8 had only ectopic endometrial tissue available, and 6 had both ectopic and eutopic endometrial tissue available for this study, providing a total of 13 eutopic and 14 ectopic endometrial samples. NIH Public AccessThe remaining 19 patients were found upon laparoscopy to have non-endometriotic ovarian cysts and thus ser...

The Role of Relaxin in Normal and Abnormal Uterine Function During the Menstrual Cycle and Early Pregnancy

“…Rxfp1 mRNA is detected in both proliferative and secretory phase endometrial samples. 52,[55][56][57] Although some studies report increased expression during the secretory phase relative to the proliferative phase, 51,52,55 others suggest constitutive expression throughout the menstrual cycle, 56,57 with considerable variation in expression among different patients. 57 In agreement with studies examining tissue expression, there was large variation in Rxfp1 mRNA expression among isolated cell cultures derived from different patients.…”

Relationship of Relaxin Hormone and Thumb Carpometacarpal Joint Arthritis

“…Relaxin, a hormone produced by the corpus luteum in pregnancy that loosens the pelvic ligaments in preparation for childbirth, has been proposed as a specific target hormone for the ligament injury and development of arthritis as a result of attenuation of the supporting joint ligaments [45]. Relaxin is a member of the insulin superfamily, produced by the uterine endometrium in nonpregnant women [15,27] and in the prostate in men [44] and has been demonstrated in postmenopausal women [3] as well. As a potential mediator of laxity in the stabilizing ligaments of the thumb CMC joint, relaxin has been shown to be present in both males and females in a circulating form [31] and a previous study showed receptors present in the anterior oblique ligaments of women [26].…”

Altered expression of activin, cripto, and follistatin in the endometrium of women with endometrioma

“…Endometriotic cysts express matrix metalloproteinases (MMP) and angiogenic factors in higher amounts with respect to eutopic endometrium, suggesting that the endometrial tissue undergoes modifications that enable its implantation in the peritoneal cavity and pelvic organs (4). Moreover, ectopic endometrium has a decreased expression of relaxin and urocortin messenger RNA (mRNA) expression, which supports a difference with eutopic tissue (5,6). Expression of estrogen and progesterone receptors is quantitatively altered in endometriotic tissue and biologically significant quantities of progesterone and estrogen are produced locally in endometriotic tissue through an abnormally active steroidogenic cascade (2).…”