Skip to Main content Skip to Navigation
Journal articles

Kisspeptin-GPR54 Signaling in Mouse NO-Synthesizing Neurons Participates in the Hypothalamic Control of Ovulation

Abstract : Reproduction is controlled in the brain by a neural network that drives the secretion of gonadotropin-releasing hormone (GnRH). Various permissive homeostatic signals must be integrated to achieve ovulation in mammals. However, the neural events controlling the timely activation of GnRH neurons are not completely understood. Here we show that kisspeptin, a potent activator of GnRH neuronal activity, directly communicates with neurons that synthesize the gaseous transmitter nitric oxide (NO) in the preoptic region to coordinate the progression of the ovarian cycle. Using a transgenic Gpr54-null IRES-LacZ knock-in mouse model, we demonstrate that neurons containing neuronal NO synthase (nNOS), which are morphologically associated with kisspeptin fibers, express the kisspeptin receptor GPR54 in the preoptic region, but not in the tuberal region of the hypothalamus. The activation of kisspeptin signaling in preoptic neurons promotes the activation of nNOS through its phosphorylation on serine 1412 via the AKT pathway and mimics the positive feedback effects of estrogens. Finally, we show that while NO release restrains the reproductive axis at stages of the ovarian cycle during which estrogens exert their inhibitory feedback, it is required for the kisspeptin-dependent preovulatory activation of GnRH neurons. Thus, interactions between kisspeptin and nNOS neurons may play a central role in regulating the hypothalamic-pituitary-gonadal axis in vivo.
Document type :
Journal articles
Complete list of metadata

https://www.hal.inserm.fr/inserm-03204468
Contributor : Vincent Prevot <>
Submitted on : Wednesday, April 21, 2021 - 3:22:47 PM
Last modification on : Thursday, September 9, 2021 - 5:24:43 PM
Long-term archiving on: : Thursday, July 22, 2021 - 6:52:10 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

N. Hanchate, J. Parkash, N. Bellefontaine, D. Mazur, W. Colledge, et al.. Kisspeptin-GPR54 Signaling in Mouse NO-Synthesizing Neurons Participates in the Hypothalamic Control of Ovulation. Journal of Neuroscience, Society for Neuroscience, 2012, 32 (3), pp.932-945. ⟨10.1523/JNEUROSCI.4765-11.2012⟩. ⟨inserm-03204468⟩

Share

Metrics

Record views

30