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GnRH release into the hypophyseal portal blood of the ewe mirrors both pulsatile and continuous intravenous infusion of kisspeptin: an insight into kisspeptin's mechanism of action.
MedLine Citation:
PMID:  23387514     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Recent studies demonstrated that kisspeptin (Kp) administration, given as a slow constant infusion of Kp10 (the shortest endogenous form of the kp molecules which carries biological activity), is able to stimulate gonadotrophin secretion and induce ovulation in anoestrus acyclic ewes. Detailed analysis of peripheral luteinising hormone (LH) concentrations, obtained at 10 min intervals, suggested that this Kp10 treatment induced continuous release of gonadotrophins. Whether this apparent constant secretion of LH resulted from a continuous elevation of GnRH or discrete high frequency pulses could not be determined. In this study, we monitored the patterns of GnRH secreted into hypophyseal portal blood (HPB) and LH in the peripheral circulation when Kp10 was administered either as discrete pulses or by means of a continuous infusion. Samples of HPB and peripheral blood were obtained at 2 and 10-min intervals, respectively, over a 6 h period, from anoestrous acyclic ewes that received an i.v. bolus injection of Kp10 at one hour and an infusion of Kp10 between hours 2 and 6. GnRH release following Kp10 administration appeared dose dependent, larger responses being seen to the 20 μg bolus and 20 μg/h infusion that the 10 μg bolus and 10μg/h infusion, the latter being marginally effective in inducing LH release. Bolus injections of Kp10 (either 20 or 10 μg) induced a sharp GnRH pulse in HPB and a discrete LH pulse in peripheral blood. In contrast constant infusion of Kp10 (either 20 or 10 μg/h for 4 h) induced a sustained increase in baseline GnRH secretion with no convincing evidence of strictly episodic release; values remained continuously elevated in HPB. No sign of pituitary desensitisation was observed at either concentration. Finally, iv injection of a large bolus (500 μg) of Kp10 produced immediate pharmacological concentrations of Kp10 in the peripheral circulation but were not associated with detectable levels of the peptide in the cerebrospinal fluid. In summary, our results demonstrate that the mode of Kp10 administration (pulsatile vs continuous) is important in shaping the pattern of GnRH secretion and suggests that this regulatory effect is most likely exerted at the level of the terminals of GnRH neurones. Moreover our data also suggest that Kp is involved in, rather than having a permissive role in, the control of endogenous GnRH pulsatility. © 2013 British Society for Neuroendocrinology.
Authors:
A Caraty; D Lomet; Sébert Me; D Guillaume; M Beltramo; Np Evans
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-7
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  -     ISSN:  1365-2826     ISO Abbreviation:  J. Neuroendocrinol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 British Society for Neuroendocrinology.
Affiliation:
UMR 7247, Physiologie de la Reproduction et des Comportements (INRA/CNRS/Université Tours/Haras Nationaux), 37380, Nouzilly, France.
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