The endogenous feeding suppressant, 2-buten-4-olide, impairs the pulsatile secretion of luteinizing hormone through endogenous opioid peptides

Department of Obstetrics and Gynecology, The University of Tokushima School of Medicine, Japan.

OBJECTIVE: To clarify the mechanism of the suppressive effect of 2-buten-4-olide (2-B4O), an endogenous feeding suppressant, on the pulsatile secretion of luteinizing hormone (LH), by studying whether endogenous opioid peptides are involved in this suppressive effect. METHODS: Using ovariectomized (ovx) rats, blood samples were taken every 6 min for 2 h after administration of 2-B4O or saline into the third cerebroventricle (3V) and sequential i.v. injection of naloxone (0. 5 mg/kg per h) or saline. Rats were divided into three experimental groups: group 1: 3V saline + i.v. saline (control); group 2: 3V 2-B4O + i.v. saline; group 3: 3V 2-B4O + i.v. naloxone. Serum LH concentrations were determined by double-antibody RIA. To determine whether 2-B4O affected the biosynthetic activity of the opioidergic neurons within the ovx rat arcuate nucleus, we measured the concentrations of pro-opiomelanocortin (POMC) mRNA, a precursor of beta-endorphin, in the rostral arcuate nucleus using non-radioactive in situ hybridization and a computerized image-analysis system. RESULTS: 2-B4O significantly suppressed the pulse frequency of LH (group 2: 1.5+/-0.33 pulses/2 h, group 1: 2.43+/-0.2 pulses/2 h; P < 0.05), but naloxone blocked its suppressive effect and restored the pulse frequency (group 3: 3.29+/-0.36 pulses/2 h, group 2: 1.5+/-0.33 pulses/2 h: P < 0.01). There were no significant changes in the mean LH concentrations and amplitude. Furthermore, 2-B4O significantly stimulated the expression of POMC mRNA in the rostral arcuate nucleus. CONCLUSION: These results suggest that 2-B4O may impair the pulsatile secretion of LH by activating the opioid pathway within the hypothalamus.