ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This study examined the regulation of thyroid hormone (TH) levels by thyrotropin-releasing hormone (TRH) neurons located in the paraventricular nucleus (PVN) of the hypothalamus in fed and fasted mice. It focused on the role of agouti-related peptide (AgRP)/neuropeptide Y (NPY) neurons in the arcuate nucleus.

Using chemogenetic activation in mice, the authors demonstrated that TRH neurons play a direct role in regulating the hypothalamic-pituitary-thyroid (HPT) axis. Activation of TRH neurons led to an increase in TSH and TH levels in both fed and fasted states, confirming their involvement in TH homeostasis. They then investigated the interaction between TRH neurons and AgRP/NPY neurons. Stimulation of AgRP/NPY neurons suppressed the HPT axis, despite increasing food intake. Inhibition of these neurons prevented the fall in TH levels during a fast, presumably via direct regulation of PVN TRH neurons via, in part, the melanocortin 4 receptor (MC4R). Additionally, the study finds that TRH-mediated feedback is independent of TH receptor beta (TRb) signaling in MC4R neurons, challenging previous hypotheses about the role of these neurons in TH regulation.

This study identifies TRH neurons as critical regulators of the hypothalamus-pituitary-thyroid axis and shows that fasting-induced TH suppression is mediated by NPY/AgRP neurons, and not - as was previously thought - by fasting-induced hypothalamic type 2 deiodinase expression and activity, increasing hypothalamic T3 production.