Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes …
CN Jayasena, GMK Nijher, OB Chaudhri… - The Journal of …, 2009 - academic.oup.com
CN Jayasena, GMK Nijher, OB Chaudhri, KG Murphy, A Ranger, A Lim, D Patel, A Mehta…
The Journal of Clinical Endocrinology & Metabolism, 2009•academic.oup.comBackground: Kisspeptin is a critical regulator of normal reproductive function. A single
injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin
release. However, the effects of kisspeptin on gonadotropin release in women with
hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to
humans are unknown. Aim: The aim of this study was to determine the effects of acute and
chronic kisspeptin administration on gonadotropin release in women with HA. Methods: We …
injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin
release. However, the effects of kisspeptin on gonadotropin release in women with
hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to
humans are unknown. Aim: The aim of this study was to determine the effects of acute and
chronic kisspeptin administration on gonadotropin release in women with HA. Methods: We …
Background: Kisspeptin is a critical regulator of normal reproductive function. A single injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin release. However, the effects of kisspeptin on gonadotropin release in women with hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to humans are unknown.
Aim: The aim of this study was to determine the effects of acute and chronic kisspeptin administration on gonadotropin release in women with HA.
Methods: We performed a prospective, randomized, double-blinded, parallel design study. Women with HA received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline (n = 5 per group) for 2 wk. Changes in serum gonadotropin and estradiol levels, LH pulsatility, and ultrasound measurements of reproductive activity were assessed.
Results: On the first injection day, potent increases in serum LH and FSH were observed after sc kisspeptin injection in women with HA (mean maximal increment from baseline within 4 h after injection: LH, 24.0 ± 3.5 IU/liter; FSH, 9.1 ± 2.5 IU/liter). These responses were significantly reduced on the 14th injection day (mean maximal increment from baseline within 4 h postinjection: LH, 2.5 ± 2.2 IU/liter, P < 0.05; FSH, 0.5 ± 0.5 IU/liter, P < 0.05). Subjects remained responsive to GnRH after kisspeptin treatment. No significant changes in LH pulsatility or ultrasound measurements of reproductive activity were observed.
Conclusion: Acute administration of kisspeptin to women with infertility due to HA potently stimulates gonadotropin release, but chronic administration of kisspeptin results in desensitization to its effects on gonadotropin release. These data have important implications for the development of kisspeptin as a novel therapy for reproductive disorders in humans.
Subcutaneous administration of kisspeptin-54 acutely and potently stimulates gonadotrophin release in women with hypothalamic amenorrhoea, but twice-daily administration over a 2-week period leads to desensitisation to its effects.
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