A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals

Animals have evolved diverse seasonal variations in physiology and reproduction to accommodate yearly changes in environmental and climatic conditions. These changes in physiology are initiated by changes in photoperiod (daylength) and are mediated through melatonin which relays photoperiodic information to the pars tuberalis of the pituitary gland. Melatonin drives thyroid stimulating hormone transcription and synthesis in the pars tuberalis which in turn regulates thyroid hormone and retinoic acid synthesis in the tanycytes lining the third ventricle of the hypothalamus. Seasonal variation in central thyroid hormone signalling is conserved among photoperiodic animals. Despite this, different species adopt divergent phenotypes to cope with the same seasonal changes. A common response amongst different species is increased hypothalamic cell proliferation/neurogenesis in short photoperiod. That cell proliferation/neurogenesis may be important for seasonal timing is based on 1) the neurogenic potential of tanycytes, 2) the fact that they are the locus of striking seasonal morphological changes and 3) the similarities to mechanisms involved in de novo neurogenesis of energy balance neurons. We propose that a fall in hypothalamic thyroid hormone and retinoic acid signalling initiates localised neurodegeneration and apoptosis which leads to a reduction in appetite and body weight. Neurodegeneration induces compensatory cell proliferation from the neurogenic niche in tanycytes and new cells are born under short photoperiod. Since these cells have the potential to differentiate into a number of different neuronal phenotypes, this could provide a mechanistic basis to explain the seasonal regulation of energy balance as well as reproduction. This cycle can be achieved without changes in thyroid hormone/retinoic acid and explains recent data from seasonal animals held in natural conditions. However, thyroid/retinoic acid signalling are required to synchronise the cycles of apoptosis, proliferation and differentiation. Thus, hypothalamic neurogenesis provides a framework to explain diverse photoperiodic responses.