Comparison of the effects of peripherally administered kisspeptins.
Mikkelsen. Jens D JD; Bentsen. Agnete H AH; Ansel. Laura L; Simonneaux. Valerie V; Juul. Anders A
Key Findings
- Peripheral mouse and human kisspeptin‑10 and longer forms increase serum testosterone in adult male mice
- Human kisspeptin‑10 and kisspeptin‑54 are as potent as mouse peptides
- Longer kisspeptin forms have slower onset but more prolonged testosterone elevation
- The testosterone rise is blocked by a GnRH antagonist, indicating an upstream pituitary mechanism
- Other related RFRP peptides do not affect testosterone
Practical Outcomes
- Kisspeptin shows promise as a peripheral way to boost testosterone, which could interest biohackers aiming for performance or body‑composition gains. However, the data are limited to acute mouse studies, with no human dosing or safety information, so it’s not ready for real‑world use yet. More research is needed before any protocol can be recommended.
Summary
In male mice, giving kisspeptin peptides (both short 10‑amino‑acid and longer versions) under the skin quickly raises blood testosterone, and the human versions work just as well as the mouse ones. Longer peptides act a bit slower but keep testosterone up longer, and the effect depends on the body’s GnRH system, not directly on the brain cells that make GnRH.
Abstract
Kisspeptins are structurally closely related peptides derived from the Kiss1 gene that have been demonstrated to stimulate the hypothalamo-pituitary gonadal axis. The natural peptide products derived from post-translational processing of the kisspeptin precursor have not been elucidated. We examined the acute effect on serum levels of free testosterone in the adult male mouse after systemic administration of kisspeptins with different lengths of both human and mouse origin. Mouse kisspeptin-10 and -52 dose-dependently increased serum testosterone, and both peptides showed similar potency and efficacy. Human kisspeptin-10 and kisspeptin-54 evoked robust increase in serum testosterone, with the same potency as for mouse kisspeptins. Other members of the RFRP family of peptides, i.e. RFRP-1 and -3 were inactive. Time-course experiments revealed that the longer forms had a slower onset of action, and the long human form also a more prolonged effect. The effect of the peripherally administered mouse kisspeptin-10 could be totally blocked by the GnRH antagonist acyline. Finally, peripherally administered mouse kisspeptin-10 had no effect on Fos induction in GnRH cells. These data show that all peptides tested are active and supports the concept that their effect is mediated by a target upstream of the pituitary, such as the median eminence.
Study Information
pubmed
2008
2008-10-10T00:00:00.000Z
10.1016/j.regpep.2008.10.001
82
39