Maintenance of the thyroid axis by leptin through actions on the TRH neuron in the PVN of the hypothalamus. A sufficient level of leptin signaling is needed to maintain TRH expression in the hypothalamic PVN, which is necessary for normal production of TSH and production of thyroid hormones by the thyroid. Two mechanisms may be involved. In one, leptin regulates arcuate neurons expressing proopiomelanocortin (POMC) (induced by leptin) and AgRP (suppressed by leptin). These arcuate neurons project to TRH neurons, where they influence TRH expression by antagonistic actions of α-MSH (stimulatory) and AgRP (inhibitory) on MC4Rs. Leptin may also act directly on TRH neurons through leptin receptors on these cells. In the absence of leptin signaling, the feedback loop between T4/T3 and the hypothalamus-pituitary-thyroid system is lost. Hence, although levels of T4/T3 may be low, TRH and TSH levels remain suppressed.