Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, United Kingdom.
J Clin Endocrinol Metab. 2011 Dec;96(12):E1963-72. doi: 10.1210/jc.2011-1408. Epub 2011 Oct 5.
Kisspeptin peptides are critical in human reproductive physiology and are potential therapies for infertility. Kisspeptin-10 stimulates gonadotropin release in both male and female rodents. However, few studies have investigated the effects of kisspeptin-10 on gonadotropin release in humans, and none have investigated the effect in women. If kisspeptin is to be useful for treating reproductive disease, its effects in both men and women must be established.
To compare the effects of kisspeptin-10 administration on reproductive hormone release in healthy men and women.
Intravenous bolus kisspeptin-10 was administered to men and women (n = 4-5 per group). Subcutaneous bolus and i.v. infusion of kisspeptin-10 was also administered to female women (n = 4-5 per group). Circulating reproductive hormones were measured.
In healthy men, serum LH and FSH were elevated after i.v. bolus kisspeptin-10, at doses as low as 0.3 and 1.0 nmol/kg, respectively. In healthy women during the follicular phase of the menstrual cycle, no alterations in serum gonadotropins were observed after i.v. bolus, s.c. bolus, or i.v. infusion of kisspeptin-10 at maximal doses of 10 nmol/kg, 32 nmol/kg, and 720 pmol/kg/min, respectively. In women during the preovulatory phase, serum LH and FSH were elevated after i.v. bolus kisspeptin-10 (10 nmol/kg).
Kisspeptin-10 stimulates gonadotropin release in men as well as women during the preovulatory phase of menstrual cycle but fails to stimulate gonadotropin release in women during the follicular phase. The sexual dimorphism of the responsiveness of healthy men and women to kisspeptin-10 administration has important clinical implications for the potential of kisspeptin-10 to treat disorders of reproduction.
kisspeptin 肽在人类生殖生理学中至关重要,是治疗不孕不育的潜在疗法。 kisspeptin-10 可刺激雄性和雌性啮齿动物的促性腺激素释放。然而,很少有研究调查 kisspeptin-10 对人类促性腺激素释放的影响,也没有研究调查其对女性的影响。如果 kisspeptin 对治疗生殖疾病有用,那么就必须确定它在男性和女性中的作用。
比较 kisspeptin-10 给药对健康男性和女性生殖激素释放的影响。
对男性和女性(每组 4-5 人)静脉内推注 kisspeptin-10。也对女性(每组 4-5 人)皮下推注和静脉内输注 kisspeptin-10。测量循环生殖激素。
在健康男性中,静脉内推注 kisspeptin-10 后,血清 LH 和 FSH 升高,剂量分别低至 0.3 和 1.0 nmol/kg。在健康女性的卵泡期,静脉内推注、皮下推注或静脉内输注 kisspeptin-10 的最大剂量分别为 10 nmol/kg、32 nmol/kg 和 720 pmol/kg/min 时,血清促性腺激素均无变化。在女性的排卵前期,静脉内推注 kisspeptin-10(10 nmol/kg)后血清 LH 和 FSH 升高。
kisspeptin-10 可刺激男性和女性在月经周期排卵前期促性腺激素释放,但不能刺激女性在卵泡期促性腺激素释放。健康男性和女性对 kisspeptin-10 给药反应的性别二态性对 kisspeptin-10 治疗生殖障碍的潜在应用具有重要的临床意义。