Abstract
BackgroundWomen treated with gonadotropin-releasing hormone (GnRH) analogs may develop enteric neuropathy and dysmotility. Administration of a GnRH analog to rats leads to similar degenerative neuropathy and ganglioneuritis. The aim of this study on rat was to evaluate the early GnRH-induced enteric neuropathy in terms of distribution of neuronal subpopulations and gastrointestinal (GI) function.MethodsForty rats were given the GnRH analog buserelin (20 μg, 1 mg/ml) or saline subcutaneously, once daily for 5 days, followed by 3 weeks of recovery, representing one treatment session. Two weeks after the fourth treatment session, the animals were tested for GI transit time and galactose absorption, and fecal weight and fat content was analyzed. After sacrifice, enteric neuronal subpopulations were analyzed. Blood samples were analyzed for zonulin and antibodies against GnRH and luteinizing hormone, and their receptors.ResultsBuserelin treatment transiently increased the body weight after 5 and 9 weeks (p < 0.001). Increased estradiol in plasma and thickened uterine muscle layers indicate high estrogen activity. The numbers of both submucous and myenteric neurons were reduced by 27%–61% in ileum and colon. The relative numbers of neurons containing calcitonin gene-related peptide (CGRP), cocaine- and amphetamine-related transcript (CART), galanin, gastrin-releasing peptide (GRP), neuropeptide Y (NPY), nitric oxide synthase (NOS), serotonin, substance P (SP), vasoactive intestinal peptide (VIP) or vesicular acetylcholine transporter (VAchT), and their nerve fiber density, were unchanged after buserelin treatment, but the relative number of submucous neurons containing somatostatin tended to be increased (p = 0.062). The feces weight decreased in buserelin-treated rats (p < 0.01), whereas feces fat content increased (p < 0.05), compared to control rats. Total GI transit time, galactose absorption, zonulin levels in plasma, and antibody titers in serum were unaffected by buserelin treatment.ConclusionsA marked enteric neuronal loss with modest effects on GI function is found after buserelin treatment. Increased feces fat content is suggested an early sign of dysfunction.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-014-0209-7) contains supplementary material, which is available to authorized users.
Highlights
Women treated with gonadotropin-releasing hormone (GnRH) analogs may develop enteric neuropathy and dysmotility
A subgroup of patients treated with gonadotropin-releasing hormone (GnRH) analogs develops enteric neuropathy with reduced relative number of GnRH-containing neurons and dysmotility [1,2], and increased abdominal pain and exacerbation of irritable bowel syndrome (IBS) has been observed in a cohort of GnRH-treated women at follow-up, no obvious dysmotility was at hand
The luteinizing hormone (LH) kit was unusable on rat plasma and serum, as no standard curve could be constructed
Summary
Women treated with gonadotropin-releasing hormone (GnRH) analogs may develop enteric neuropathy and dysmotility. A subgroup of patients treated with gonadotropin-releasing hormone (GnRH) analogs develops enteric neuropathy with reduced relative number of GnRH-containing neurons and dysmotility [1,2], and increased abdominal pain and exacerbation of irritable bowel syndrome (IBS) has been observed in a cohort of GnRH-treated women at follow-up, no obvious dysmotility was at hand [3]. This knowledge rendered us to set up an experimental rat model to examine the effects on the gastrointestinal (GI) tract of systemic and repeated treatment with the GnRH analog buserelin. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
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