Fasting results in reduced
thyroid hormone levels and inappropriately low or normal
thyroid-stimulating hormone (TSH), partly attributed to
central hypothyroidism due to suppression of
pro TRH gene expression in the hypothalamic paraventricular nucleus. Recently, we demonstrated that the systemic administration of
leptin to fasting animals restores plasma
thyroxine (T4) and proTRH
mRNA in the paraventricular nucleus to normal, suggesting that the fall in circulating
leptin levels during fasting acts as a signal to hypophysiotropic neurons in the paraventricular nucleus to reset the set point for feedback regulation of
pro TRH mRNA by
thyroid hormone. To determine whether the effect of fasting on the hypothalamic-pituitary-thyroid axis is mediated through the hypothalamic arcuate nucleus where
leptin receptors are highly concentrated, we studied the effect of fasting and exogenous
leptin administration on plasma
thyroid hormone levels and proTRH
mRNA concentration in the paraventricular nucleus in adult animals with arcuate nucleus lesions induced pharmacologically by the neonatal administration of monosodium
L-glutamate (
MSG). In normal animals, fasting reduced plasma T4 and TSH levels and the concentration of proTRH
mRNA in the hypothalamic paraventricular nucleus. In contrast, neither fasting nor
leptin administration to fasting
MSG-treated animals had any significant effects on plasma
thyroid hormone and TSH levels and proTRH
mRNA in the paraventricular nucleus. These studies suggest that during fasting, the arcuate nucleus is essential for the normal homeostatic response of the hypothalamic-pituitary-thyroid axis and may serve as a critical locus to mediate the central actions of
leptin on proTRH gene expression in the paraventricular nucleus.