RT Journal Article
SR Electronic
T1 The Role of Kisspeptin–GPR54 Signaling in the Tonic Regulation and Surge Release of Gonadotropin-Releasing Hormone/Luteinizing Hormone
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12088
OP 12095
DO 10.1523/JNEUROSCI.2748-07.2007
VO 27
IS 44
A1 Heather M. Dungan
A1 Michelle L. Gottsch
A1 Hongkui Zeng
A1 Alexander Gragerov
A1 John E. Bergmann
A1 Demetrios K. Vassilatis
A1 Donald K. Clifton
A1 Robert A. Steiner
YR 2007
UL http://www.jneurosci.org/content/27/44/12088.abstract
AB The Kiss1 gene codes for kisspeptin, which binds to GPR54, a G-protein-coupled receptor. Kisspeptin and GPR54 are expressed in discrete regions of the forebrain, and they have been implicated in the neuroendocrine regulation of reproduction. Kiss1-expressing neurons are thought to regulate the secretion of gonadotropin-releasing hormone (GnRH) and thus coordinate the estrous cycle in rodents; however, the precise role of kisspeptin–GPR54 signaling in the regulation of gonadotropin secretion is unknown. In this study, we used female mice with deletions in the GPR54 gene [GPR54 knock-outs (KOs)] to test the hypothesis that kisspeptin–GPR54 signaling provides the drive necessary for tonic GnRH/luteinizing hormone (LH) release. We predicted that tonic GnRH/LH secretion would be disrupted in GPR54 KOs and that such animals would be incapable of showing a compensatory rise in LH secretion after ovariectomy. As predicted, we found that GPR54 KO mice do not exhibit a postovariectomy rise in LH, suggesting that tonic GnRH secretion is disrupted in the absence of kisspeptin–GPR54 signaling. We also postulated that kisspeptin–GPR54 signaling is critical for the generation of the estradiol (E)-induced GnRH/LH surge and thus E should be incapable of inducing an LH surge in the absence of GPR54. However, we found that E induced Fos expression in GnRH neurons and produced a GnRH-dependent LH surge in GPR54 KOs. Thus, in mice, kisspeptin–GPR54 signaling is required for the tonic stimulation of GnRH/LH secretion but is not required for generating the E-induced GnRH/LH surge.