Neuropeptide Y has a central inhibitory action on the hypothalamic-pituitary-thyroid axis

Recent evidence suggests that neuropeptide Y (NPY), originating in neurons in the hypothalamic arcuate nucleus, is an important mediator of the effect s of leptin on the central nervous system. As these NPY neurons innervate h ypophysiotropic neurons in the hypothalamic paraventricular nucleus (PVN) t hat produce the tripeptide, TRH, we raised the possibility that NPY may be responsible for resetting of the hypothalamic-pituitary-thyroid (HPT) axis during fasting. To test this hypothesis, the effects of intracerebroventric ularly administered NPY on circulating thyroid hormone levels and proTRH me ssenger RNA in the PVN were studied by RIA and in situ hybridization histoc hemistry, respectively. NPY administration suppressed circulating levels of thyroid hormone (T, and T,) and resulted in an inappropriately normal or l ow TSH. These alterations were associated with a significant suppression of proTRH messenger RNA in the PVN, indicating that NPY infusion had resulted in a state of central hypothyroidism. Similar observations were made in NP Y-infused animals pair fed to the vehicle-treated controls. These data are reminiscent of the effect of fasting on the thyroid axis and indicate that NPY may play a major role in the inhibition of HPT axis during fasting.