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estradiol-17 beta
conditional gene targeting
kiss1
arcuate nucleus
anteroventral periventricular nucleus
luteinizing-hormone secretion
hypogonadotropic hypogonadism
postnatal-development
feedback mechanism
negative feedback
gene-expression
release
activation
estradiol
kiss-1
Science & Technology - Other Topics
Abstract:
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 alpha (ER alpha) 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 ERa 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 ER alpha in two separate kisspeptin neuronal populations in the hypothalamus.
