EFFECTS OF 2-BUTEN-4-OLIDE, AN ENDOGENOUS FEEDING SUPPRESSANT, ON THE PULSATILE SECRETION OF LUTEINIZING-HORMONE IN OVARIECTOMIZED RATS

The effects of 2-buten-4-olide (2-B4O). an endogenous feeding suppressant. on the secretion of luteinizing hormone (LH) were studied in ovariectomized rats. Intraperitoneal (ip) administration of 2-B4O: adult female ovariectomized Wistar rats were given daily ip injections of solution containing 2-B4O at 0, 50 or 100 mg/kg body wt for 14 days. This ip treatment with 2-B4O significantly decreased the mean LH concentration and pulse frequency of LH. Intravenous (iv) administration of 2-B4O: a solution of 2-B4O (50 or 100 mg/kg body wt) was slowly injected through an intra-atrium catheter and blood samples were taken every 6 min for 2 h. This iv treatment significantly suppressed the LH pulse frequency but had no significant effect on the LH amplitude or mean LH. Injection of 2-B4O into the third cerebroventricle: the injection of 2-B4O into the third cerebroventricle of freely moving rats decreased the mean LH concentration and the frequency and amplitude of LH pulses. Third cerebroventricle injection of a corticotropin-releasing factor (CRF) receptor antagonist before third cerebroventricle injection of 2-B4O: the specific CRF receptor antagonist alpha-helical-CRF (9-41) was injected into the third cerebroventricle of ovariectomized rats before injection of 2-B4O. Administration of 2-B4O into the third cerebroventricle significantly decreased the mean LH, concentration and pulse frequency. Third cerebroventricle injection of the CRF antagonist at 50 mug/rat and then 2-B4O also resulted in significant suppression of the mean LH concentration and pulse frequency. These findings suggest that 2-B4O may suppress gonadotropin-releasing hormone secretion in ovariectomized rats and that its effect in decreasing LH pulses may not be caused through the CRF pathway.