Interaction of gonadotropin-releasing hormone with the gastrointestinal tract: experimental and clinical perspectives

Gonadotropin-releasing hormone (GnRH) is a key regulator of the hypothalamic–pituitary–gonadal axis. Emerging evidence indicates its involvement in the regulation of somatic functions, including those of the gastrointestinal tract (GIT), which is attributable to the presence of GnRH receptors within gastrointestinal tissues. Objective. To perform a systematic literature search in the PubMed database, followed by a comprehensive analysis and synthesis of findings from contemporary studies examining the interactions between GnRH and the digestive system. Key points. GnRH receptors have been identified throughout the gastrointestinal tract, supporting the possibility of direct hormonal effects. In the liver, GnRH is involved in the regulation of lipid and carbohydrate metabolism, as well as fibrogenesis; however, data on the clinical safety of its analogues remain inconsistent. In the stomach, GnRH modulates secretory activity and cellular proliferation, likely via vagally mediated mechanisms. In the intestine, its role in regulating the enteric nervous system and gut microbiota is under investigation, although findings are conflicting. In the pancreas, GnRH is presumed to influence glycemic control and hormonal secretion. The detection of GnRH receptors in tumors of the digestive system underscores the potential for developing targeted therapeutic strategies. Conclusion. GnRH should be regarded as an intersystem regulator linking reproductive and metabolic pathways with gastrointestinal function. The limited and inconsistent nature of the available evidence highlights the need for further fundamental and clinical studies to elucidate the mechanisms of action and clinical relevance of GnRH.