Leuprolide acetate affects intestinal motility in female rats before and after ovariectomy

Abstract

Leuprolide acetate, a gonadotropin-releasing hormone (GnRH) analogue, is currently being proposed to control debilitating symptoms in women with functional bowel disease. Whether leuprolide alters gastrointestinal motility as part of its actions is unknown. This study was designed to assess, using myoelectric techniques in an animal model, the effects of leuprolide on potential mechanisms of neuromuscular function of small intestine. Female rats with (n = 6) or without (n = 8) bilateral ovariectomy were used to study jejunal motility before and after leuprolide therapy. Throughout the study, daily leuprolide dosages of 0.02, 0.2, or 0.4 micrograms/kg were injected into intact rats and 0.02, 0.2, 0.4, 1.0, or 2.5 micrograms/kg into ovariectomized rats. Recordings were made while the rats were fasted and postprandial and before and after leuprolide administration. Under control conditions, migrating myoelectric complexes (MMCs) were found in intact female rats, whether fasted or postprandial. After ovariectomy, postprandial controls and those treated with low-dose leuprolide (0.02, 0.2, and 0.4 micrograms) had typical fed-state patterns and no MMCs, but at 1.0 and 2.5 micrograms the fed state was inhibited and cycling MMCs occurred at a frequency similar to that of fasted controls. Reproductive hormones thus have a significant effect on gastrointestinal motility.