EFFECTS OF AN ANTISENSE OLIGODEOXYNUCLEOTIDE FOR NEUROPEPTIDE-Y MESSENGER-RNA ON IN-VIVO LUTEINIZING-HORMONE-RELEASING HORMONE-RELEASE IN OVARIECTOMIZED FEMALE RHESUS-MONKEYS

The present study examines the effects of an antisense oligodeoxynucle otide (AS) for human neuropeptide Y (NPY) mRNA on in vivo LHRH release using the push-pull perfusion method in female ovariectomized monkeys . After 6 h of control perfusion, 10 mu M Of the AS NPY was infused fo r 8 h, which was followed by an additional 4 h of control perfusion. A s a control for AS, an oligodeoxynucleotide containing the same bases in a scrambled sequence (SC) was similarly examined. LHRH and NPY leve ls in perfusate samples, collected in 10-min fractions, were measured by RIA. AS NPY infusion resulted in a significant decrease in mean NPY release starting 2 h after the initiation of infusion, and continuing until shortly after the end of AS infusion (P < 0.05, n = 7). AS NPY also suppressed mean LHRH release significantly (P < 0.05, n = 7): the AS NPY-induced LHRH suppression started 2 h after the initiation of A S infusion, and continued throughout AS infusion, lasting for the enti re period of the experiment. In contrast, SC NPY resulted in neither s ignificant changes in NPY release nor LHRH release. These data suggest that NPY release in the stalk-median eminence plays an important role in the control of pulsatile release of LHRH in vivo in the rhesus mon key. (C) 1998 Elsevier Science BN. All rights reserved.