Mammalian circannual pacemakers

Circannual clocks drive rhythms in reproduction and many other seasonal characteristics but the underlying control of these long-term oscillators remains a mystery. Now, we propose that circannual timing involves mechanisms that are integral to the ontogenetic life-history programme where annual transitions are generated by cell birth, death and tissue regeneration throughout the life cycle--the histogenesis hypothesis. The intrinsic cycle is then timed by cues from the environment. The concept is that in specific sites in the brain, pituitary and peripheral tissues, residual populations of progenitor cells (adult stem cells) synchronously initiate a phase of cell division to begin a cycle. The progeny cells then proliferate, migrate and differentiate, providing the substrate that drives physiological change over long time-spans (e.g. summer/winter); cell death may be required to trigger the next cycle. We have begun to characterise such a tissue-based timer in our Soay sheep model focusing on the pars tuberalis (PT) of the pituitary gland and the sub-ventricular zone of the mediobasal hypothalamus (MBH) as potential circannual pacemakers. The PT is of special interest because it is a melatonin-responsive tissue containing undifferentiated cells, strategically located at the gateway between the brain and pituitary gland. The PT also governs long-photoperiod activation of thyroid hormone dependant processes in the MBH required for neurogenesis. In sheep, exposure to long photoperiod markedly activates BrDU-labelled cell proliferation in the PT and MBH, and acts to entrain the circannual reproductive cycle. Variation in expression and co-ordination of multiple tissue timers may explain species differences in circannual rhythmicity. This paper is dedicated to the memory of Ebo Gwinner.