Inhibitory effects of the new bombesin receptor antagonist RC-3095 on the luteinizing hormone release in rats

The effects of bombesin receptor antagonist RC-3095 and gastrin-releasing peptide [GRP (14-27)] on basal luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels, as well as on the release of LH and FSH in response to LH-releasing hormone, were studied in normal and castrated male rats. We also examined the release of LH and FSH after intracerebroventricular injection of RC-3095 under different types of anesthesia (urethane, sodium pentobarbital, Metofane). Following injection of 10 micrograms RC-3095 into the lateral brain ventricle, serum LH levels were rapidly and significantly (p < 0.001) lowered. This effect lasted for at least 60 min and was not affected by the type of anesthetic used. Serum FSH levels were not affected by intracerebroventricular administration of RC-3095 or GRP (14-27), indicating different central control mechanisms between LH and FSH release. The suppressive effect of RC-3095 on LH release could be completely prevented by prior intracerebroventricular administration of GRP (14-27) at a dose of 1 micrograms, but intravenous administration of either peptide RC-3095 or GRP (14-27) did not change the basal levels of LH, FSH, and testosterone. The pituitary LH response to LH-releasing hormone was also not modified by intravenous administration of RC-3095. These results indicate that bombesin-like peptides might be involved in control of LH release from the pituitary by an action on the CNS which is mediated by specific bombesin receptors.