An Increase in Kisspeptin-54 Release Occurs with the Pubertal Increase in Luteinizing Hormone-Releasing Hormone-1 Release in the Stalk-Median Eminence of Female Rhesus Monkeys in Vivo

• Published in: Endocrinology (Philadelphia) Vol. 149; no. 8; pp. 4151 - 4157
• Main Authors: Keen, Kim L, Wegner, Frederick H, Bloom, Stephen R, Ghatei, Mohammad A, Terasawa, Ei
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.08.2008; The Endocrine Society
• Subjects: Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; Gonadotropin-Releasing Hormone - metabolism; Kisspeptins; Macaca mulatta - metabolism; Macaca mulatta - physiology; Median Eminence - metabolism; Microdialysis; Oligopeptides - administration & dosage; Oligopeptides - pharmacology; Pulsatile Flow - drug effects; Sexual Maturation - drug effects; Sexual Maturation - physiology; Time Factors; Tumor Suppressor Proteins - metabolism; Tumor Suppressor Proteins - physiology; Vertebrates: endocrinology; Puberty; Monkey; Gonadotropin RH; Hypothalamic hormone; Kisspeptin; In vivo; Vertebrata; Mammalia; Primates; Median eminence; Female; Hormone releasing factor; Release
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2008-0231

The G-protein coupled receptor GPR54 and its ligand, KiSS-1-derived peptide kisspeptin-54, appear to play an important role in the mechanism of puberty. This study measures the release of kisspeptin-54 in the stalk-median eminence (S-ME) during puberty and examines its potential role in the pubertal increase in LHRH-1 release in female rhesus monkeys. First, developmental changes in release of kisspeptin-54 and LHRH-1 were assessed in push-pull perfusate samples obtained from the S-ME of prepubertal, early pubertal, and midpubertal female rhesus monkeys. Whereas LHRH-1 levels in 10-min intervals had been measured previously for other experiments, kisspeptin-54 levels in 40-min pooled samples were newly measured by RIA. The results indicate that a significant increase in kisspeptin-54 release occurred in association with the pubertal increase in LHRH-1 release and that a nocturnal increase in kisspeptin-54 release was already observed in prepubertal monkeys and continued through the pubertal period. Second, we measured kisspeptin-54 release in the S-ME of midpubertal monkeys at 10-min intervals using a microdialysis method. Kisspeptin-54 release in the S-ME was clearly pulsatile with an interpulse interval of about 60 min, and approximately 75% of kisspeptin-54 pulses were correlated with LHRH-1 pulses. Finally, the effect of kisspeptin-10 on LHRH-1 release was examined with the microdialysis method. Kisspeptin-10 infusion through a microdialysis probe significantly stimulated LHRH-1 release in a dose-dependent manner. Collectively, the results are consistent with the hypothesis that kisspeptin plays a role in puberty.