Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 6, Pages 2129-2134Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0409822102
Keywords
gonadotropin-releasing hormone; GPR54; kisspeptins; monkey; development; hypothalamus
Categories
Funding
- NCRR NIH HHS [P51 RR000163, RR00163, K01 RR000163] Funding Source: Medline
- NICHD NIH HHS [R01 HD015788, U54 HD029164, U54 HD008610, U54 HD018185, HD13254, P30 HD008610, U54 HD028138, P30 HD018185, R01 HD025123, HD28138, HD18185, R01 HD043341, HD25123, R01 HD013254, P30 HD028138, P50 HD028138, HD08610] Funding Source: Medline
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To further study the role of GPR54 signaling in the onset of primate puberty, we used the monkey to examine the ability of kisspeptin-10 to elicit the release of gonadotropin-releasing hormone (GnRH) precociously, and we describe the expression of GPR54 and KiSS-1 in the hypothalamus during the peripubertal period. Agonadal juvenile male monkeys were implanted with a lateral cerebroventricular cannula and a jugular vein catheter. The responsiveness of the juvenile pituitary to endogenous GnRH release was heightened with a chronic pulsatile i.v. infusion of synthetic GnRH before kisspeptin-10 (112-121) injection. Intracerebroventricular (30 mug or 100 mug) or i.v. (100 mug) bolus injections of kisspeptin-10 elicited a robust GnRH discharge, as reflected by luteinizing hormone secretion, which was abolished by pretreatment with a GnRH-receptor antagonist. RNA was isolated from the hypothalamus of agonadal males before (juvenile) and after (pubertal) the pubertal resurgence of pulsatile GnRH release and from juvenile, early pubertal, and midpubertal ovary-intact females. KiSS-1 mRNA levels detected by real-time PCR increased with puberty in both male and female monkeys. In intact females, but not in agonadal males, GPR54 mRNA levels in the hypothalamus increased approximate to3-fold from the juvenile to midpubertal stage. Hybridization histochemistry indicated robust KiSS-1 and GPR54 mRNA expression in the region of the arcuate nucleus. These findings are consistent with the hypothesis that GPR54 signaling by its cognate ligand in the primate hypothalamus may be activated at the end of the juvenile phase of development and may contribute to the pubertal resurgence of pulsatile GnRH release, the central drive for puberty.
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