title: Oestrogen-independent circadian clock gene expression in the anteroventral periventricular nucleus in female rats: possible role as an integrator for circadian and ovarian signals timing the luteinising hormone surge.
abstract: Periodic ovulation in rats, mice and hamsters is the result of a surge in luteinising hormone (LH) that depends on circadian gating signals emerging from the master circadian clock within the suprachiasmatic nucleus (SCN) and rising ovarian oestrogen levels. These two signals converge into the anteroventral periventricular nucleus (AVPV) and lead to the release of kisspeptin, which is responsible for surges of gonadotrophin-releasing hormone and, in turn, of LH release. How the AVPV integrates circadian and reproductive signals remains unclear. In the present study, we show that the female rat AVPV itself shows circadian oscillations in the expression of the clock genes PER1 and BMAL1, which lie at the core circadian clockwork of mammals. In ovariectomised females treated with oestradiol (E₂), these oscillations are in synchrony with the AVPV rhythmic expression of the KISS1 gene and the gene that codes for the arginine-vasopressin (AVP) receptor AVPr1a. Although clock gene oscillations are independent of oestrogen levels, circadian expression of Kiss1 and Avpr1a (also referred to as V1a) mRNA is blunted and absent, respectively, in ovariectomised animals without E₂ replacement. Because AVP is considered to be a critical SCN transmitter to gate the LH surge, our data suggest that there is a circadian oscillator located in the AVPV, and that such a putative oscillator could, in an oestrogen-dependent manner, time the sensitivity to circadian signals emerging from the SCN and the release of kisspeptin.
authors.affiliation: Department of Biology, University of Washington, Seattle, WA, USA.|Program of Neurobiology and Behavior, University of Washington, Seattle, WA, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Smarr
authors.affiliation: Department of Biology, University of Washington, Seattle, WA, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Gile
authors.affiliation: Department of Biology, University of Washington, Seattle, WA, USA.|Program of Neurobiology and Behavior, University of Washington, Seattle, WA, USA.
authors.forename: H O
authors.initials: HO
authors.lastname: de la Iglesia
mesh_terms: D000818:Animals; D001483:Base Sequence; D057906:Circadian Clocks / Q000235:genetics*; D017931:DNA Primers; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007032:Hypothalamus, Anterior / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000502:physiology*; D010053:Ovary / Q000502:physiology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar
chemical_list: D017931:DNA Primers; D004967:Estrogens; D007986:Luteinizing Hormone
keywords: circadian oscillators; kisspeptin; ovulation; vasopressin
references.citation: PLoS One. 2013 Jul 22;8(7):e68793
references.pmid: 23894346
references.citation: Curr Biol. 2004 May 4;14(9):796-800
references.pmid: 15120072
references.citation: Endocrinology. 2011 Feb;152(2):595-606
references.pmid: 21190958
references.citation: Endocrinology. 2012 Jun;153(6):2839-50
references.pmid: 22454148
references.citation: J Neuroendocrinol. 1993 Apr;5(2):137-44
references.pmid: 8485548
references.citation: J Neuroendocrinol. 1999 Jul;11(7):481-90
references.pmid: 10444305
references.citation: J Comp Neurol. 2001 May 7;433(3):312-34
references.pmid: 11298358
references.citation: Curr Biol. 2009 May 26;19(10):848-52
references.pmid: 19375313
references.citation: Cell Tissue Res. 2002 Jul;309(1):89-98
references.pmid: 12111539
references.citation: Methods Mol Biol. 2007;362:513-31
references.pmid: 17417038
references.citation: J Neurosci. 2002 Jan 1;22(1):350-6
references.pmid: 11756518
references.citation: J Neurosci. 2006 Nov 22;26(47):12219-25
references.pmid: 17122046
references.citation: Endocrinology. 2006 Mar;147(3):1148-53
references.pmid: 16373412
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17540-5
references.pmid: 19805128
references.citation: Endocr Rev. 2010 Aug;31(4):544-77
references.pmid: 20237240
references.citation: J Comp Neurol. 1997 Aug 11;384(4):569-79
references.pmid: 9259490
references.citation: J Neuroendocrinol. 2010 Sep;22(9):1032-9
references.pmid: 20584108
references.citation: Brain Res. 2001 May 18;901(1-2):109-16
references.pmid: 11368957
references.citation: Neuroreport. 1995 Sep 11;6(13):1715-22
references.pmid: 8541467
references.citation: Endocrinology. 2009 Aug;150(8):3664-71
references.pmid: 19443569
references.citation: Mol Cell Endocrinol. 2011 Jun 6;339(1-2):90-7
references.pmid: 21458520
references.citation: Neuroscience. 1999;94(1):141-50
references.pmid: 10613504
references.citation: Neuroscience. 1999;93(2):659-66
references.pmid: 10465449
references.citation: J Endocrinol. 1980 Feb;84(2):231-6
references.pmid: 6444980
references.citation: Physiol Rev. 2012 Jul;92(3):1235-316
references.pmid: 22811428