title: Evidence for a Putative Circadian Kiss-Clock in the Hypothalamic AVPV in Female Mice.
abstract: The kisspeptin (Kp) neurons in the anteroventral periventricular nucleus (AVPV) are essential for the preovulatory LH surge, which is gated by circulating estradiol (E2) and the time of day. We investigated whether AVPV Kp neurons in intact female mice may be the site in which both E2 and daily signals are integrated and whether these neurons may host a circadian oscillator involved in the timed LH surge. In the afternoon of proestrous day, Kp immunoreactivity displayed a marked and transient decrease 2 hours before the LH surge. In contrast, Kp content was stable throughout the day of diestrus, when LH levels are constantly low. AVPV Kp neurons expressed the clock protein period 1 (PER1) with a daily rhythm that is phase delayed compared with the PER1 rhythm measured in the main clock of the suprachiasmatic nuclei (SCN). PER1 rhythm in the AVPV, but not in the SCN, exhibited a significant phase delay of 2.8 hours in diestrus as compared with proestrus. Isolated Kp-expressing AVPV explants from PER2::LUCIFERASE mice displayed sustained circadian oscillations of bioluminescence with a circadian period (23.2 h) significantly shorter than that of SCN explants (24.5 h). Furthermore, in AVPV explants incubated with E2 (10 nM to 1 μM), the circadian period was lengthened by 1 hour, whereas the SCN clock remained unaltered. In conclusion, these findings indicate that AVPV Kp neurons display an E2-dependent daily rhythm, which may possibly be driven by an intrinsic circadian clock acting in combination with the SCN timing signal.
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives (Unité Propre de Recherche, Centre National de la Recherche Scientifique, Unité 3212); Université de Strasbourg, 67084 Strasbourg, France.
authors.forename: David
authors.initials: D
authors.lastname: Chassard
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives (Unité Propre de Recherche, Centre National de la Recherche Scientifique, Unité 3212); Université de Strasbourg, 67084 Strasbourg, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bur
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives (Unité Propre de Recherche, Centre National de la Recherche Scientifique, Unité 3212); Université de Strasbourg, 67084 Strasbourg, France.
authors.forename: Vincent-Joseph
authors.initials: VJ
authors.lastname: Poirel
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives (Unité Propre de Recherche, Centre National de la Recherche Scientifique, Unité 3212); Université de Strasbourg, 67084 Strasbourg, France.
authors.forename: Jorge
authors.initials: J
authors.lastname: Mendoza
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives (Unité Propre de Recherche, Centre National de la Recherche Scientifique, Unité 3212); Université de Strasbourg, 67084 Strasbourg, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Simonneaux
mesh_terms: D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000378:metabolism*; D057906:Circadian Clocks / Q000235:genetics*; D004031:Diestrus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011359:Proestrus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000378:metabolism
chemical_list: D059648:Kisspeptins; D004958:Estradiol