Relationship of reproductive hormones and neuromuscular disease of the gastrointestinal tract

Functional disorders of the gastrointestinal tract comprise a common but ill-defined group of diseases; they primarily afflict women. Although predominantly involving nerve and muscle, the cellular and molecular bases of the pathogenesis of these functional disorders are unknown. Clinical studies indicate that some result from neural dysfunction within the enteric nervous system, others may be due to muscular problems, and the causes of still others remain unknown. Laboratory studies have shown that ovarian products such as progesterone, luteinizing hormone, human chorionic gonadotropin, and relaxin (but not estrogen), are neural antagonists of gastrointestinal motility. The production and secretion of these ovarian substances are controlled by gonadotropin-releasing hormone (GnRH) released from the hypothalamus; they probably act on gamma-aminobutyric acid receptors and alter chloride influx into the cell. GnRH analogs are effective drugs that downmodulate the hypothalamic-pituitary-gonadal axis and inhibit the secretion of gonadal products involved in such hormone-dependent diseases as endometriosis and prostate cancer. Acting on the GnRH receptors (seven transmembrane domain receptors) on myenteric neurons, GnRH analogs are also effective neural modulators in such disorders as functional bowel disease. These analogs are a promising new group of compounds that may be used to treat difficult gastrointestinal problems.