Kisspeptins (KPs) and their receptor (GPR54 or KiSS1R) play a key-role in regulation of the
hypothalamic-pituitary-gonadal axis and are therefore interesting targets for therapeutic interventions
in the field of reproductive endocrinology. As dogs show a rapid and robust LH response
after the administration of KP10, they can serve as a good animal model for research concerning
KP signaling. The aims of the present study were to test the antagonistic properties of KP analogs
p234, p271, p354, and p356 in vitro, by determining the intracellular Ca2+ response of
CHEM1 cells that stably express human GPR54, and to study the in vivo effects of these peptides
on basal plasma LH concentration and the KP10-induced LH response in female dogs.
Exposure of the CHEM1 cells to KP-10 resulted in a clear Ca2+ response. P234, p271, p354,
and p356 did not prevent or lower the KP10-induced Ca2+ response. Moreover, the in vivo studies
in the dogs showed that none of these supposed antagonists lowered the basal plasma LH
concentration and none of the peptides lowered the KP10-induced LH response. In conclusion,
p234, p271, p354, and p356 had no antagonistic effects in vitro nor any effect on basal and kisspeptin-
stimulated plasma LH concentration in female dogs.
S1 Dataset. CHEM1-GPR54 fluorescence before and after adition of canine KP10, human
KP-10, p234, p271, p354 and p356.
S2 Dataset. Plasma LH concentration in anestrous bitches before, during and after canine
KP10, p271, p354 and p356 administration.