Lincoln G A, Hazlerigg D G
University of Edinburgh, Centre for Reproductive Biology, Queen's Medical Research Institute, Edinburgh EH16 4T.
Soc Reprod Fertil Suppl. 2010;67:171-86.
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.
年周期生物钟驱动着繁殖及许多其他季节性特征的节律，但这些长期振荡器的潜在控制机制仍是个谜。现在，我们提出年周期定时涉及到个体发育生命史程序中不可或缺的机制，在整个生命周期中，年度转变是由细胞生成、死亡和组织再生产生的——即组织发生假说。然后，内在周期由来自环境的线索定时。其概念是，在大脑、垂体和外周组织的特定部位，祖细胞（成体干细胞）的残余群体同步启动细胞分裂阶段以开始一个周期。子代细胞随后增殖、迁移并分化，提供驱动长时间跨度（如夏季/冬季）生理变化的底物；可能需要细胞死亡来触发下一个周期。我们已开始在我们的索艾羊模型中对这样一种基于组织的定时器进行表征，重点关注垂体的结节部（PT）和中基底下丘脑（MBH）的室下区，将其作为潜在的年周期起搏器。PT特别引人关注，因为它是一个对褪黑素敏感的组织，含有未分化细胞，位于大脑和垂体之间的关键位置。PT还控制着MBH中神经发生所需的甲状腺激素依赖性过程的长光周期激活。在绵羊中，暴露于长光周期会显著激活PT和MBH中溴脱氧尿苷标记的细胞增殖，并起到调整年周期繁殖周期的作用。多种组织定时器表达和协调的变化可能解释了年周期节律的物种差异。本文谨献给埃博·温纳。
