TY - JOUR
T1 - Timing and completion of puberty in female mice depend on estrogen receptor α-signaling in kisspeptin neurons
AU - Mayer, Christian
AU - Acosta-Martinez, Maricedes
AU - Dubois, Sharon L.
AU - Wolfe, Andrew
AU - Radovick, Sally
AU - Boehm, Ulrich
AU - Levine, Jon E.
PY - 2010/12/28
Y1 - 2010/12/28
N2 - 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.
AB - 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.
KW - Anteroventral periventricular nucleus
KW - Arcuate nucleus
KW - Conditional gene targeting
KW - Estradiol-17β
KW - Kiss1
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U2 - 10.1073/pnas.1012406108
DO - 10.1073/pnas.1012406108
M3 - Article
C2 - 21149719
AN - SCOPUS:78651102603
SN - 0027-8424
VL - 107
SP - 22693
EP - 22698
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 52
ER -