title: Binary Switching of Calendar Cells in the Pituitary Defines the Phase of the Circannual Cycle in Mammals.
abstract: Persistent free-running circannual (approximately year-long) rhythms have evolved in animals to regulate hormone cycles, drive metabolic rhythms (including hibernation), and time annual reproduction. Recent studies have defined the photoperiodic input to this rhythm, wherein melatonin acts on thyrotroph cells of the pituitary pars tuberalis (PT), leading to seasonal changes in the control of thyroid hormone metabolism in the hypothalamus. However, seasonal rhythms persist in constant conditions in many species in the absence of a changing photoperiod signal, leading to the generation of circannual cycles. It is not known which cells, tissues, and pathways generate these remarkable long-term rhythmic processes. We show that individual PT thyrotrophs can be in one of two binary states reflecting either a long (EYA3(+)) or short (CHGA(+)) photoperiod, with the relative proportion in each state defining the phase of the circannual cycle. We also show that a morphogenic cycle driven by the PT leads to extensive re-modeling of the PT and hypothalamus over the circannual cycle. We propose that the PT may employ a recapitulated developmental pathway to drive changes in morphology of tissues and cells. Our data are consistent with the hypothesis that the circannual timer may reside within the PT thyrotroph and is encoded by a binary switch timing mechanism, which may regulate the generation of circannual neuroendocrine rhythms, leading to dynamic re-modeling of the hypothalamic interface. In summary, the PT-ventral hypothalamus now appears to be a prime structure involved in long-term rhythm generation.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Shona H
authors.initials: SH
authors.lastname: Wood
authors.affiliation: Department of Physiology, Anatomy, and Genetics, Le Gros Clark Building, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Christian
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9PRG, UK.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Miedzinska
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Ben R C
authors.initials: BR
authors.lastname: Saer
authors.affiliation: Department of Physiology, Anatomy, and Genetics, Le Gros Clark Building, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Johnson
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9PRG, UK.
authors.forename: Bob
authors.initials: B
authors.lastname: Paton
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9PRG, UK.
authors.forename: Le
authors.initials: L
authors.lastname: Yu
authors.affiliation: MRC Centre for Reproductive Health, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: McNeilly
authors.affiliation: Faculty of Medical and Human Science, University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Julian R E
authors.initials: JR
authors.lastname: Davis
authors.affiliation: MRC Centre for Reproductive Health, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
authors.forename: Alan S
authors.initials: AS
authors.lastname: McNeilly
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9PRG, UK. Electronic address: dave.burt@roslin.ed.ac.uk.
authors.forename: David W
authors.initials: DW
authors.lastname: Burt
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: andrew.loudon@manchester.ac.uk.
authors.forename: Andrew S I
authors.initials: AS
authors.lastname: Loudon
mesh_terms: D000818:Animals; D057906:Circadian Clocks; D008297:Male; D017440:Photoperiod; D012756:Sheep / Q000502:physiology*; D052684:Thyrotrophs / Q000502:physiology*