Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54.

Autor:	Jayasena CN; Section of Investigative Medicine (C.N.J., A.A., A.N.C., R.R., A.D.S., G.M.K.N., Z.G.-D., M.A.G., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Department of Imaging (A.M., C.T.), Imperial College Healthcare National Health Service Trust, Charing Cross Hospital, London W6 8RF, United Kingdom., Abbara A, Veldhuis JD, Comninos AN, Ratnasabapathy R, De Silva A, Nijher GM, Ganiyu-Dada Z, Mehta A, Todd C, Ghatei MA, Bloom SR, Dhillo WS
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2014 Jun; Vol. 99 (6), pp. E953-61. Date of Electronic Publication: 2014 Feb 11.
DOI:	10.1210/jc.2013-1569
Abstrakt:	Background: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. Aim: The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Methods: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Results: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 1.6 ± 0.4, vehicle; 5.0 ± 0.5, kisspeptin-54, P < .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P < .05 vs vehicle). Conclusions: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.
Databáze:	MEDLINE
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