Natural peptides displaying agonist activity on the orphan G protein-coupled receptor GPR54 were isolated from human placenta. These 54, 14 and 13 aminoacid peptides, with a common RF-amide C-terminus, derive from the product of KiSS-1, a metastasis suppressor gene for melanoma cells, and were therefore designated kisspeptins. They bound with low nanomolar affinities to rat and human GPR54 expressed in CHO-K1 cells, and stimulated PIP2 hydrolysis, Ca2+ mobilization, arachidonic acid release, ERK1/2 and p38 MAPK phosphorylation and stress fiber formation, but inhibited cell proliferation. Human GPR54 was highly expressed in placenta, pituitary, pancreas and spinal cord, suggesting a role in the regulation of endocrine function. Stimulation of oxytocin secretion following kisspeptin administration to rats confirmed this hypothesis.

Masato Kotani et al., Papers In Press, published online ahead of print July 16, 2001, J. Biol. Chem, 10.1074/jbc.M104847200