title: Temporal expression of seven clock genes in the suprachiasmatic nucleus and the pars tuberalis of the sheep: evidence for an internal coincidence timer.
abstract: The 24-h expression of seven clock genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2, and CK1 epsilon ) was assayed by in situ hybridization in the suprachiasmatic nucleus (SCN) and the pars tuberalis (PT) of the pituitary gland, collected every 4 h throughout 24 h, from female Soay sheep kept under long (16-h light/8-h dark) or short (8-h light/16-h dark) photoperiods. Locomotor activity was diurnal, inversely related to melatonin secretion, and prolactin levels were increased under long days. All clock genes were expressed in the ovine SCN and PT. In the SCN, there was a 24-h rhythm in Clock expression, in parallel with Bmal1, in antiphase with cycles in Per1 and Per2; there was low-amplitude oscillation of Cry1 and Cry2. The waveform of only Per1 and Per2 expression was affected by photoperiod, with extended elevated expression under long days. In the PT, the high-amplitude 24-h cycles in the expression of Bmal1, Clock, Per1, Per2, Cry1, and Cry2, but not CK1 epsilon, were influenced by photoperiod. Per1 and Per2 peaked during the day, whereas Cry1 and Cry2 peaked early in the night. Hence, photoperiod via melatonin had a marked effect on the phase relationship between Per/Cry genes in the PT. This supports the conclusion that an "external coincidence model" best explains the way photoperiod affects the waveform of clock gene expression in the SCN, the central pacemaker, whereas an "internal coincidence model" best explains the way melatonin affects the phasing of clock gene expression in the PT to mediate the photoperiodic control of a summer or winter physiology.
authors.affiliation: Medical Research Council, Human Reproductive Sciences Unit, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, UK. g.lincoln@hrsu.mrc.ac.uk
authors.forename: Gerald
authors.initials: G
authors.lastname: Lincoln
authors.forename: Sophie
authors.initials: S
authors.lastname: Messager
authors.forename: Håkan
authors.initials: H
authors.lastname: Andersson
authors.forename: David
authors.initials: D
authors.lastname: Hazlerigg
mesh_terms: D056930:ARNTL Transcription Factors; D000222:Adaptation, Physiological; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks / Q000235:genetics*; D056926:CLOCK Proteins; D047388:Casein Kinases; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000235:genetics; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005260:Female; D005420:Flavoproteins / Q000235:genetics; D015870:Gene Expression; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D056950:Period Circadian Proteins; D017440:Photoperiod; D017956:Photoreceptor Cells, Invertebrate; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D012621:Seasons; D012756:Sheep; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D047388:Casein Kinases; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D011494:Protein Kinases; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; D014157:Transcription Factors; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C538963:CRY1 protein, human; C538966:CRY2 protein, human; C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; C513312:Per2 protein, mouse; C119828:cry protein, Drosophila; C538943:CLOCK protein, human; C538944:Clock protein, mouse