Timing and completion of puberty in female mice depend on estrogen receptor α-signaling in kisspeptin neurons

Christian Mayer, Maricedes Acosta-Martinez, Sharon L. Dubois, Andrew Wolfe, Sally Radovick, Ulrich Boehm, Jon E. Levine

Research output: Contribution to journalArticlepeer-review


Puberty onset is initiated by activation of neurons that secrete gonadotropin-releasing hormone (GnRH). The timing and progression of puberty may depend upon temporal coordination of two opposing central mechanisms - a restraint of GnRH secretion before puberty onset, followed by enhanced stimulation of GnRH release to complete reproductive maturation during puberty. Neuronal estrogen receptor α (ERα) has been implicated in both controls; however, the underlying neural circuits are not well understood. Here we test whether these mechanisms are mediated by neurons that express kisspeptin, a neuropeptide that modulates GnRH neurosecretion. Strikingly, conditional ablation of ERα in kisspeptin neurons results in a dramatic advancement of puberty onset in female mice. Furthermore, subsequent pubertal maturation is arrested in these animals, as they fail to acquire normal ovulatory cyclicity. We show that the temporal coordination of juvenile restraint and subsequent pubertal activation is likely mediated by ERα in two separate kisspeptin neuronal populations in the hypothalamus.

Original languageEnglish (US)
Pages (from-to)22693-22698
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
StatePublished - Dec 28 2010
Externally publishedYes


  • Anteroventral periventricular nucleus
  • Arcuate nucleus
  • Conditional gene targeting
  • Estradiol-17β
  • Kiss1

ASJC Scopus subject areas

  • General


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