title: Delayed pubertal onset and prepubertal Kiss1 expression in female mice lacking central oestrogen receptor beta.
abstract: Ovarian oestradiol is essential for pubertal maturation and adult physiology of the female reproductive axis. It acts at central and peripheral sites through two main oestrogen receptors (ER) α and β. Here we investigate the role of ERβ on central effects of oestradiol, by generating a mouse line specifically lacking the ERβ gene in neuronal and glial cells. Central ERβ deletion delays the age at vaginal opening and first oestrous and reduces uterine weight without affecting body growth. Analysis of factors necessary for pubertal progression shows reduced levels of Kiss1 transcripts at postnatal (P) day 25 in the preoptic area, but not in the mediobasal hypothalamus (MBH) of mutant females. In agreement with these data, the number of kisspeptin-immunoreactive neurons was decreased by 57-72% in the three subdivisions of the rostral periventricular area of the third ventricle (RP3V), whereas the density of kisspeptin-immunoreactive fibres was unchanged in the arcuate nucleus of mutant mice. These alterations do not involve changes in ERα mRNAs in the preoptic area and protein levels in the RP3V. The number and distribution of GnRH-immunoreactive cells were unaffected, but gonadotropin-releasing hormone (GnRH) transcript levels were higher in the P25 preoptic area of mutants. At adulthood, mutant females have normal oestrous cyclicity, kisspeptin system and exhibit unaltered sexual behaviour. They display, however, reduced ovary weight and increased anxiety-related behaviour during the follicular phase. This argues for the specific involvement of central ERβ in the regulation of pubertal onset in female reproduction, possibly through prepubertal induction of kisspeptin expression in the RP3V.
authors.affiliation: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France, Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Naulé
authors.affiliation: Institut National de la Recherche Agronomique, UMR 85, Nouzilly, France, Centre National de la Recherche Scientifique, UMR 7247, Nouzilly, France, Université François Rabelais, Tours, France, Institut Français du Cheval et de l'Equitation, Nouzilly, France and.
authors.forename: Vincent
authors.initials: V
authors.lastname: Robert
authors.affiliation: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France, Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Parmentier
authors.affiliation: Institut National de la Recherche Agronomique, UMR 85, Nouzilly, France, Centre National de la Recherche Scientifique, UMR 7247, Nouzilly, France, Université François Rabelais, Tours, France, Institut Français du Cheval et de l'Equitation, Nouzilly, France and.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Martini
authors.affiliation: Institut National de la Recherche Agronomique, UMR 85, Nouzilly, France, Centre National de la Recherche Scientifique, UMR 7247, Nouzilly, France, Université François Rabelais, Tours, France, Institut Français du Cheval et de l'Equitation, Nouzilly, France and.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Keller
authors.affiliation: Inserm U1132 and university Paris-Diderot, Hospital Lariboisière, Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Cohen-Solal
authors.affiliation: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France, Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Hardin-Pouzet
authors.affiliation: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France, Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Grange-Messent
authors.affiliation: Institut National de la Recherche Agronomique, UMR 85, Nouzilly, France, Centre National de la Recherche Scientifique, UMR 7247, Nouzilly, France, Université François Rabelais, Tours, France, Institut Français du Cheval et de l'Equitation, Nouzilly, France and.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Franceschini
authors.affiliation: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France, Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, Paris, France, sakina.mhaouty-kodja@upmc.fr.
authors.forename: Sakina
authors.initials: S
authors.lastname: Mhaouty-Kodja
mesh_terms: D000818:Animals; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011627:Puberty / Q000235:genetics / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D059648:Kisspeptins; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol