Repetitive activation of hypothalamic G protein-coupled receptor 54 with intravenous pulses of kisspeptin in the juvenile monkey (Macaca mulatta) elicits a sustained train of gonadotropin-releasing hormone discharges.

Abstract:

:The purpose of the present study was to further examine the hypothesis that activation of G protein-coupled receptor 54 (GPR54) signaling at the end of the juvenile phase of primate development is responsible for initiation of gonadarche and the onset of puberty. Accordingly, we determined whether repetitive iv administration of the GPR54 receptor agonist kisspeptin-10 (2 microg as a brief 1-min infusion once every hour for 48 h) to the juvenile male rhesus monkey would prematurely elicit sustained, pulsatile release of hypothalamic GnRH, the neuroendocrine trigger for gonadarche. GnRH release was monitored indirectly by measuring LH secretion from the in situ pituitary, the GnRH responsiveness of which had been heightened before the experiment with an intermittent iv infusion of synthetic GnRH. Agonadal animals (n = 4) were employed to eliminate any confounding and secondary effects of changing feedback signals from the testis. The first brief infusion of kisspeptin-10 evoked an LH discharge that mimicked those produced by GnRH priming, and this was followed by a train of similar LH discharges in response to hourly activation of GPR54 by repetitive kisspeptin-10 administration. Concomitant treatment with a GnRH receptor antagonist, acyline, abolished kisspeptin-10-induced LH release. Repetitive kisspeptin-10 administration also provided a GnRH-dependent signal to FSH secretion. These findings are consistent with the notion that, in primates, the transition from the juvenile (attenuated GnRH release) to pubertal (robust GnRH release) state is controlled by activation of GPR54 resulting from increased expression of hypothalamic KiSS-1 and release of kisspeptin in this region of the brain.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Plant TM,Ramaswamy S,Dipietro MJ

doi

10.1210/en.2005-1261

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

1007-13

issue

2

eissn

0013-7227

issn

1945-7170

pii

en.2005-1261

journal_volume

147

pub_type

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