A synthetic kisspeptin analog that triggers ovulation and advances puberty

Abstract : The neuropeptide kisspeptin and its receptor, KiSS1R, govern the reproductive timeline of mammals by triggering puberty onset and promoting ovulation by stimulating gonadotrophin-releasing hormone (GnRH) secretion. To overcome the drawback of kisspeptin short half-life we designed kisspeptin analogs combining original modifications, triazole peptidomimetic and albumin binding motif, to reduce proteolytic degradation and to slow down renal clearance, respectively. These analogs showed improved in vitro potency and dramatically enhanced pharmacodynamics. When injected intramuscularly into ewes (15 nmol/ewe) primed with a progestogen, the best analog (compound 6, C6) induced synchronized ovulations in both breeding and non-breeding seasons. Ovulations were fertile as demonstrated by the delivery of lambs at term. C6 was also fully active in both female and male mice but was completely inactive in KiSS1R KO mice. Electrophysiological recordings of GnRH neurons from brain slices of GnRH-GFP mice indicated that C6 exerted a direct excitatory action on GnRH neurons. Finally, in prepubertal female mice daily injections (0.3 nmol/mouse) for five days significantly advanced puberty. C6 ability to trigger ovulation and advance puberty demonstrates that kisspeptin analogs may find application in the management of livestock reproduction and opens new possibilities for the treatment of reproductive disorders in humans.
Document type :
Journal articles
Complete list of metadatas

Cited literature [43 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-01406943
Contributor : Isabelle Frapart <>
Submitted on : Tuesday, September 26, 2017 - 9:33:40 PM
Last modification on : Tuesday, June 4, 2019 - 4:30:06 PM

File

2016_Decourt_ScientificReports...
Explicit agreement for this submission

Identifiers

Collections

Citation

Caroline Decourt, Vincent Robert, Karine Anger, Mathieu Galibert, Jean-Baptiste Madinier, et al.. A synthetic kisspeptin analog that triggers ovulation and advances puberty. Scientific Reports, Nature Publishing Group, 2016, 6, pp.26908. ⟨10.1038/srep26908⟩. ⟨hal-01406943⟩

Share

Metrics

Record views

247

Files downloads

100