Abstract
Puberty onset is initiated in the brain by activation of gonadotropin-releasing hormone (GnRH) neurosecretion. Different permissive signals must be integrated for the initiation of reproductive maturation; however, the neural circuits controlling timely awakening of the reproductive axis are not understood. The identification of the neuropeptide kisspeptin as a potent activator of GnRH neuronal activity suggests that kisspeptin-releasing neurons might coordinate puberty onset. To test this hypothesis, we generated mice that specifically lack kisspeptin cells. Puberty onset in females was unaffected by kisspeptin neuron ablation. Furthermore, the animals were fertile, albeit with smaller ovaries. Consistent with this, female mice lacking neurons that express the kisspeptin receptor GPR54 were also fertile. Acute ablation of kisspeptin neurons in adult mice inhibited fertility, suggesting that there is compensation for the loss of kisspeptin neurons early in development. Our data indicate that the initiation and completion of reproductive maturation can occur in the absence of kisspeptin/GPR54 signaling.
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Acknowledgements
We are indebted to O. Pongs for continuous support. A. Marquardt and D. Drexler provided expert technical assistance. We thank R. Kühn for providing the IGD3.2 embryonic stem cells and A. Waisman for providing the R26-iDTR mice, I. Hermans-Borgmeyer for help with embryonic stem cell work and blastocyst injections, A. Derin and U. Wolters for animal caretaking, B. Mann for performing the hormone assays and M. Roberson and K. Duncan for helpful discussions. This project was supported by Deutsche Forschungsgemeinschaft grant BO1743/2 to U.B.
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C.M. and U.B. designed the experiments. C.M. carried out most of the experiments. C.M. and U.B. analyzed the data. U.B. conceived the project and wrote the paper.
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Mayer, C., Boehm, U. Female reproductive maturation in the absence of kisspeptin/GPR54 signaling. Nat Neurosci 14, 704–710 (2011). https://doi.org/10.1038/nn.2818
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DOI: https://doi.org/10.1038/nn.2818
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