The endocrine control of the onset of thermogenesis at birth

The experimental studies in the fetal sheep demonstrate that the central hypothalamic mechanisms for responding to a cold stress have differentiated well before birth. There are several major determinants of the initiation of maximal thermogenesis at birth. These are cutaneous cooling, oxygenation and separation from the placenta. Firstly the stimulation of cutaneous cold receptors regulates sympathetic nervous system activity, primarily local noradrenaline release from sympathetic nerve termini to the brown adipocyte adrenoreceptors. Circulating catecholamines, the euthyroid state and other hormones also play a role. Secondly an increase in oxygen delivery to brown adipose tissue through increased oxygen content and increased blood flow is required. Finally, our observations suggest that separation from the placenta is necessary for maximal nonshivering thermogenesis. The effects on thermogenesis of interrupting and reestablishing placental flow are rapid and reversible. Umbilical cord occlusion is the signal for a rapid increase in thermogenesis, while the release of cord occlusion is followed by an equally rapid fall in thermogenesis. This strongly suggests the presence of a placental inhibitor of brown adipose tissue thermogenesis. The problem of the regulation of growth and recruitment of brown adipose tissue in the fetus despite the lack of thermal stress in utero may be resolved by this evidence for an inhibitory factor of thermogenesis produced by the placenta. The withdrawal of the inhibitor at birth by separation from the placenta will allow the rapid initiation of thermogenesis in response to sympathetic nervous system stimulation of the brown adipose tissue.