Study summary · research use only
A kisspeptin-10 analog with greater in vivo bioactivity than kisspeptin-10
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this mouse study, the authors examined a modified kisspeptin-10 (KP-10) analog. They describe kisspeptins as neuropeptides that stimulate the hypothalamo-pituitary-gonadal (HPG) axis, with the smallest endogenous form KP-10 binding the receptor KISS1R with similar affinity to full-length kisspeptin-54 but showing weaker action in vivo. Structurally modified KP-10 analogs were tested for KISS1R binding affinity, ERK1/2 phosphorylation in vitro, and HPG-axis stimulation in vivo. The abstract reports that one analog, [dY]1KP-10, bound KISS1R with lower affinity than KP-10 but showed similar in vitro bioactivity, and that peripheral administration increased plasma LH and testosterone more potently than KP-10 at 20 min postinjection in mice. At 60 min, 0.15 nmol [dY]1KP-10 significantly increased total testosterone, whereas the same dose of KP-10 had no significant effect.
Abstract
The kisspeptins are neuropeptides that stimulate the hypothalamo-pituitary-gonadal (HPG) axis. The smallest endogenous kisspeptin, kisspeptin-10 (KP-10), binds to the receptor KISS1R with a similar affinity to the full-length peptide, kisspeptin-54 (KP-54), but is less effective in vivo, possibly because of increased enzymatic breakdown or clearance. The kisspeptin system may have therapeutic potential in the treatment of reproductive disorders and endocrine cancers. We have rationally modified the structure of KP-10 and tested the binding affinity of these analogs for the KISS1R. Those analogs that bound with relatively high affinity to KISS1R were tested for ability to stimulate ERK1/2 phosphorylation in vitro and for their ability to stimulate the HPG axis in vivo. One analog, [dY](1)KP-10, bound to KISS1R with lower affinity to KP-10 and exhibited similar bioactivity in vitro. However, in vivo peripheral administration of [dY](1)KP-10 increased plasma LH and testosterone more potently than KP-10 itself at 20 min postinjection in mice. In addition, 60 min postinjection, 0.15 nmol [dY](1)KP-10 significantly increased total testosterone levels in mice whereas the same dose of KP-10 had no significant effect. Should manipulation of the kisspeptin/KISS1R signaling system prove therapeutically useful, long-lasting analogs such as [dY](1)KP-10 may have greater therapeutic potential than endogenous forms of kisspeptin.
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