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Gonadotrophin‐Releasing Hormone Release into the Hypophyseal Portal Blood of the Ewe Mirrors Both Pulsatile and Continuous Intravenous Infusion of K isspeptin: An Insight into K isspeptin's Mechanism of Action
Author(s) -
Caraty A.,
Lomet D.,
Sébert M. E.,
Guillaume D.,
Beltramo M.,
Evans N. P.
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12030
Subject(s) - endocrinology , medicine , bolus (digestion) , pulsatile flow , kisspeptin , ovulation , luteinizing hormone , gonadotropin releasing hormone , peripheral , hormone , endogeny , peptide hormone , chemistry
Recent studies have demonstrated that kisspeptin ( K p) administration, given as a slow constant infusion of K p10 (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 K p10 treatment induced the continuous release of gonadotrophins. Whether this apparent constant secretion of LH resulted from a continuous elevation of G n RH or discrete high‐frequency pulses could not be determined. In the present study, we monitored the patterns of gonadotrophin‐releasing homrone ( G n RH) secreted into hypophyseal portal blood ( HPB ) and LH in the peripheral circulation when K p10 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 K p10 at 1 h and an infusion of K p10 between hours 2 and 6. G n RH release following K p10 administration appeared to be dose‐dependent, with larger responses being seen to the 20 μg bolus and 20 μg/h infusion than to the 10 μg bolus and 10 μg/h infusion, with the latter being marginally effective in inducing LH release. Bolus injections of K p10 (either 20 or 10 μg) induced a sharp G n RH pulse in HPB and a discrete LH pulse in peripheral blood. By contrast, constant infusion of K p10 (either 20 or 10 μg/h for 4 h) induced a sustained increase in baseline G n RH 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, i.v. injection of a large bolus (500 μg) of K p10 produced immediate pharmacological concentrations of K p10 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 K p10 administration (pulsatile versus continuous) is important in shaping the pattern of G n RH secretion and suggests that this regulatory effect is most likely exerted at the level of the terminals of G n RH neurones. Moreover our data also suggest that K p is involved in, rather than having a permissive role in, the control of endogenous G n RH pulsatility.