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Obstetrical & Gynecological Survey:
doi: 10.1097/01.ogx.0000251011.40001.96
Gynecology: Reproductive Biology

Kisspeptin-54 Stimulates the Hypothalamic-Pituitary Gonadal Axis in Human Males

Dhillo, Waljit S.; Chaudhri, Owais B.; Patterson, Michael; Thompson, Emily L.; Murphy, Kevin G.; Badman, Michael K.; McGowan, Barbara M.; Amber, Vian; Patel, Sejal; Ghatei, Mohammad A.; Bloom, Stephen R.

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Abstract

Kisspeptin is a 54-amino acid peptide that activates the G protein-coupled receptor GPR54. This system appears to be an important regulator of reproduction. Mutation of GPR54 is associated with failed reproductive function. Studies in rodents and primates indicate that the endogenous neuropeptide agonist for GPR54, kisspeptin, strongly stimulates the hypothalamic-pituitary-gonadal axis. This double-blind, placebo-controlled, crossover study examined the effects of elevated circulating levels of kisspeptin on testosterone and gonadotropin concentrations in six males who received 90-minute intravenous infusions of 4 pmol/kg/minute of kisspeptin-54 and physiological saline in random order.

Increasing infusion rates of kisspeptin-54 led to a dose-dependent rise in mean plasma kisspeptin immunoreactivity (IR). A dose-dependent increase in luteinizing hormone (LH) levels also was documented. Mean levels of follicle-stimulating hormone (FSH) also increased over time as kisspeptin-54 was infused, and there was a trend toward increased plasma testosterone levels. The increases in FSH and testosterone, however, were not dose-dependent. Elevations in circulating levels of LH, FSH, and testosterone were significant compared with responses to saline infusion. Infusion of kisspeptin-54 had no effect on the release of inhibin B or on sexual arousal scores. The course of kisspeptin-IR after reaching a plateau level followed first-order kinetics with a plasma half-life of 27 minutes, a mean metabolic clearance rate of 3.2 m/kg/minute, and a volume of distribution of 128 ml/kg.

Systemic administration of kisspeptin-54 acutely increases circulating levels of gonadotropins and testosterone in human males. This potentially provides a novel means of manipulating the hypothalamic-pituitary-gonadal axis in patients with reproductive disorders.

© 2007 Lippincott Williams & Wilkins, Inc.

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