Effects of an antisense oligodeoxynucleotide for neuropeptide Y mRNA on in vivo luteinizing hormone-releasing hormone release in ovariectomized female rhesus monkeys.
The present study examines the effects of an antisense oligodeoxynucleotide (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 microM of the AS NPY was infused for 8 h, which was followed by an additional 4 h of control perfusion. As a control for AS, an oligodeoxynucleotide containing the same bases in a scrambled sequence (SC) was similarly examined. LHRH and NPY levels 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 AS infusion, and continued throughout AS infusion, lasting for the entire period of the experiment. In contrast, SC NPY resulted in neither significant 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 monkey.
Kasuya
E
E
Wisconsin Regional Primate Research Center, University of Wisconsin-Madison, 53715-1299, USA.
Mizuno
M
M
Watanabe
G
G
Terasawa
E
E
D000818:Animals; D001483:Base Sequence; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics*
D009478:Neuropeptide Y; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone