Kisspeptin-10

In healthy men, intravenous bolus kisspeptin-10 produced a rapid, dose-dependent rise in serum LH, with maximal stimulation at 1 ug/kg. Continuous lower-dose infusion (1.5 ug/kg/h) increased mean LH, raised LH pulse frequency (approximately 0.7 to 1.0 pulses/h), and increased secretory burst mass, with a downstream rise in testosterone. The data indicate kisspeptin-10 acts upstream of GnRH to augment pulsatile gonadotropin secretion.

When healthy men were given kisspeptin-10 into a vein, their luteinizing hormone (LH) — the pituitary signal that drives testosterone — rose quickly and in proportion to the dose. A slow infusion also made LH pulses come more often and testosterone rise. This was an early human study showing the peptide can switch on the reproductive hormone axis.

Kisspeptin-10 stimulated gonadotropin (LH and FSH) release in healthy men across doses. In women, the gonadotropin response was strongly dependent on menstrual cycle phase: robust during the preovulatory phase but largely absent during the follicular phase. This demonstrates sexual dimorphism and sex-steroid/cycle-dependent sensitivity of the human hypothalamic-pituitary-gonadal axis to kisspeptin-10.

Kisspeptin-10 reliably raised reproductive hormones in men, but in women its effect depended heavily on where they were in their menstrual cycle — working near ovulation but not in the early follicular phase. This showed that men and women respond differently, and that the female response shifts with the hormonal state of the cycle.

In a randomized, double-blind, placebo-controlled crossover fMRI study of 29 healthy heterosexual young men, kisspeptin administration enhanced activity in limbic and paralimbic brain structures in response to sexual and couple-bonding images. The degree of enhancement correlated with psychometric measures of reward, drive, and reduced sexual aversion, and kisspeptin attenuated negative mood. Findings suggest a central role for kisspeptin in integrating sexual and emotional processing beyond its endocrine effects. (This study used the kisspeptin-54 isoform.)

Brain scans of healthy young men showed that kisspeptin boosted activity in emotional and reward-related brain regions when they viewed sexual and romantic images, and it slightly improved mood. The effects tracked with how the men rated their own arousal and mood. This suggested kisspeptin influences the emotional and sexual brain, not just reproductive hormones, and hinted at possible use in psychosexual disorders.