title: Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons.
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 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.
authors.affiliation: Institute for Neural Signal Transduction, Center for Molecular Neurobiology, D-20253 Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mayer
authors.forename: Maricedes
authors.initials: M
authors.lastname: Acosta-Martinez
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Dubois
authors.forename: Andrew
authors.initials: A
authors.lastname: Wolfe
authors.forename: Sally
authors.initials: S
authors.lastname: Radovick
authors.forename: Ulrich
authors.initials: U
authors.lastname: Boehm
authors.forename: Jon E
authors.initials: JE
authors.lastname: Levine
mesh_terms: D000818:Animals; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology*; D030762:Estrous Cycle; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007150:Immunohistochemistry; D059648:Kisspeptins; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D010052:Ovariectomy; D012741:Sexual Maturation / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone