Abstract
Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone, and luteinizing hormone orchestrate the reproduction cycle and regulate the sex steroid secretion from the gonads. In mammals, GnRH1 is secreted as a hormone from the hypothalamus, whereas both GnRH1 and GnRH2 are present as neurotransmitters/peptides in various tissues, where the peptides exert many different effects. mRNA coding for GnRH1 and GnRH2 have been described in the human gastrointestinal tract, and GnRH has been found in both submucosal and myenteric neurons. mRNA coding for GnRH and the fully expressed peptide have been found in rat enteric neurons by some researchers but not by others. mRNA coding for GnRH receptors, but not the fully expressed receptor, has been found in one rat study. GnRH influences gastrointestinal motility and secretion. GnRH analogs are clinically used in the treatment of sex hormone-dependent diseases, i.e., endometriosis and malignancies, and as pretreatment for in vitro fertilization. Reduced numbers of enteric neurons and IgM antibodies against GnRH and progonadoliberin-2 (precursor of GnRH2) have been observed after such treatment, with the clinical picture of gastrointestinal dysmotility. Similarly, a rat model of enteric neurodegeneration has been developed after administration of the GnRH analog buserelin. Serum IgM antibodies against GnRH1, progonadoliberin-2, and GnRH receptors have been described in patients with signs and symptoms of gastrointestinal dysmotility and/or autonomic dysfunction, such as irritable bowel syndrome, enteric dysmotility, diabetes mellitus, and primary Sjögren’s syndrome. Thus, apart from regulation of reproduction and sex hormone secretion, GnRH also constitutes a part of enteric nervous system (ENS) and its functions during physiological and pathological conditions. This review aimed to describe the role of GnRH in the ENS.
Highlights
Gonadotropin-releasing hormone (GnRH) is secreted in a pulsatile fashion from hypothalamic neurons into the portal circulation, where GnRH receptors on the anterior pituitary are activated with subsequent secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (1, 2)
IgM antibodies against GnRH1, progonadoliberin-2, and GnRH receptors may occur in a subgroup of patients with functional bowel disorders and dysmotility, both in idiopathic forms and when associated with diabetes mellitus, posterior laryngitis, primary Sjögren’s syndrome, or GnRH treatment (39, 40, 42–45)
Gonadotropin-releasing hormone has been found in the human enteric nervous system (ENS) in repeated examinations
Summary
Gonadotropin-releasing hormone (GnRH) is secreted in a pulsatile fashion from hypothalamic neurons into the portal circulation, where GnRH receptors on the anterior pituitary are activated with subsequent secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (1, 2). FSH and LH target the gonads and regulate the secretion of steroid hormones (3). GnRH and ENS is secreted into the portal circulation and has a half-life of a few minutes, the hormone levels cannot be analyzed in peripheral blood (2). Measurements of FSH and LH levels in blood are used to estimate the hypothalamic–pituitary function. GnRH1 is secreted from the hypothalamus, whereas both types are present in several organs and tissues of the body, e.g., neural tissue, where they exert neuroendocrine, paracrine, and autocrine functions in the central and peripheral nervous system (4). Several different receptors are described, only the GnRH1 receptor is expressed in mammals (3). Both GnRH1 and GnRH2 act through the GnRH1 receptor (4)
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