Central and peripheral effects of thyroid hormone signalling in the control of energy metabolism

Increasing evidence points towards a role for thyroid hormone signalling in the central nervous system with respect to the development of symptoms of thyroid disease, in addition to the well-known peripheral effects of thyroid hormone. Thyroid hormone affects target tissues directly via thyroid hormone receptors, but also indirectly through effects on the integration of the sympathetic signal in target tissues. The present review discusses these pathways and the evidence for a third pathway, that is effects of thyroid hormone on the pre-autonomic neurones in the central nervous system. The pre-autonomic neurones reside in the hypothalamus in brain nuclei such as the paraventricular nucleus of the hypothalamus where thyroid hormone receptor isoforms are expressed. Recent data from studies in transgenic mice implicate a role for thyroid hormone receptor alpha 1 in the modulation of sympathetic signalling to target tissues, thereby affecting both glucose and lipid metabolism. Focal stimulation of hypothalamic nuclei expressing thyroid hormone receptors and selective liver denervation experiments in rats have provided further evidence indicating that the metabolic changes observed during hyperthyroidism are not only a result of increased thyroid hormone signalling in the periphery, but also, at least in part, result from altered signalling in thyroid hormone sensitive neurones.