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Effects of Kisspeptin-10 on the Electrophysiological Manifestation of Gonadotropin-Releasing Hormone Pulse Generator Activity in the Female Rat

Division of Reproduction and Endocrinology (J.S.K.-J., X.F.L., K.T.O’B.), New Hunt’s House, King’s College London, Guy’s Campus, London SE1 1UL, United Kingdom; and Faculty of Life Sciences (S.M.L.), University of Manchester, Manchester M13 9PL, United Kingdom

Address all correspondence and requests for reprints to: Dr. Kevin O’Byrne, Division of Reproduction and Endocrinology, 2.36D New Hunt’s House, King’s College London, Guy’s Campus, London SE1 1UL, United Kingdom. E-mail: kevin.o'byrne{at}kcl.ac.uk.

Kisspeptins are extraordinarily potent in stimulating gonadotropic hormone secretion via an action on the hypothalamic GnRH neural system. Because the physiological frequency of the GnRH pulse generator is a critical component of the control system that governs reproductive processes, the aim of this study was to examine the effect of kisspeptin-10 on pulsatile LH secretion and on the electrophysiological manifestation of GnRH pulse generator activity to determine frequency modulatory effects. Adult Sprague Dawley rats were ovariectomized and chronically implanted with electrodes in the arcuate nucleus to record the characteristic increases in hypothalamic multiunit electrical activity volleys coincident with the initiation of each LH pulse measured in peripheral blood and/or indwelling cardiac catheters for the collection of blood samples (25 µl) every 5 min for 6–7 h for the measurement of LH. Intravenous infusion of kisspeptin-10 (7.5, 35, and 100 nmol) induced a dose-dependent increase in LH secretion. The stimulatory effect of kisspeptin-10 (100 nmol) on LH secretion was blocked by the GnRH antagonist cetrorelix, precluding a singular action on gonadotropes. Unexpectedly, however, the marked increase in LH release in response to kisspeptin-10 (100 nmol) administration was not accompanied by any change in multiunit electrical activity volley frequency. It seem unlikely, therefore, that kisspeptin-10 has an appreciable frequency modulatory effect on GnRH pulse generator activity in the female rat.

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