Gonadotropin-Releasing Hormone and Its Physiological and Pathophysiological Roles in Relation to the Structure and Function of the Gastrointestinal Tract

Abstract

Background: Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are involved in the reproductive cycle and regulate the secretion of sex steroids from the gonads. In mammals, GnRH1 is secreted as a hormone from the hypothalamus, whereas both GnRH1 and GnRH2 are present as neuropeptides in a variety of tissues. This review describes the role of GnRH in the gastrointestinal tract. Summary: GnRH1, GnRH2, and LH receptors in humans and rats, and GnRH receptors in rats, have been described in the gastrointestinal tract, where they affect motility, gastric and hormone secretion, and cell proliferation. GnRH analogs are clinically used in the treatment of sex hormone-dependent diseases, i.e., endometriosis and malignancies, and as pretreatments for in vitro fertilization. Severe gastrointestinal dysmotility has been shown to develop in some women after such treatment, along with a reduction in the number of enteric neurons and autoantibodies against GnRH. Consequently, a rat model of enteric neurodegeneration has been developed based on the administration of the GnRH analog buserelin. Serum IgM antibodies against GnRH1, the GnRH2 precursor progonadoliberin-2, and the GnRH receptor have also been described in patients with irritable bowel syndrome and dysmotility, as well as in patients with gastrointestinal disorders associated with diabetes mellitus, posterior laryngitis, and primary Sjögren's syndrome, although no treatments using GnRH analogs have been administered. Conclusion: GnRH and receptors for GnRH and LH are present in the human and rat gastrointestinal tract. Treatment with GnRH analogs may induce severe dysmotility, and a rat model of enteric neurodegeneration has been developed based on stimulation by the GnRH analog buserelin. Autoantibodies against GnRH and its receptor are found in a subgroup of patients with functional bowel disorders and dysmotility, independent of treatment with GnRH analogs.