Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis.
Jayasena. Channa N CN; Nijher. Gurjinder M K GM; Chaudhri. Owais B OB; Murphy. Kevin G KG; Ranger. Amita A; Lim. Adrian A; Patel. Daksha D; Mehta. Amrish A; Todd. Catriona C; Ramachandran. Radha R; Salem. Victoria V; Stamp. Gordon W GW; Donaldson. Mandy M; Ghatei. Mohammad A MA; Bloom. Stephen R SR; Dhillo. Waljit S WS
Key Findings
- One acute subcutaneous dose of kisspeptin (6.4âŻnmol/kg) caused a large, shortâterm rise in LH (â24âŻIU/L) and FSH (â9âŻIU/L) in women with hypothalamic amenorrhea.
- After 14 days of twiceâdaily dosing, the same injection only produced a minimal increase in LH (â2.5âŻIU/L) and FSH (â0.5âŻIU/L), showing strong tachyphylaxis.
- Despite the loss of response to kisspeptin, the womenâs pituitary still responded to a GnRH challenge, indicating the desensitization was specific to kisspeptin signaling.
Practical Outcomes
- For biohackers interested in using kisspeptin to influence reproductive hormones, a single dose can be a potent, shortâlived trigger, but repeated dosing quickly leads to tolerance, making chronic protocols ineffective. This suggests kisspeptin is not suitable for longâterm hormone modulation and should be used only for acute, experimental purposes, if at all.
Summary
A single shot of kisspeptin under the skin can quickly raise the hormones that trigger ovulation (LH and FSH) in women who have stopped having periods because their brain isnât signaling the reproductive system. However, giving the same dose twice a day for two weeks makes the body stop responding, so the hormone boost disappears.
Abstract
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. The aim of this study was to determine the effects of acute and chronic kisspeptin administration on gonadotropin release in women with HA. 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. 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. 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.
Study Information
pubmed
2009
2009-10-09T00:00:00.000Z
10.1210/jc.2009-0406
197
39