Small, specific subpopulations of hypothalamic neurons play a major role in regulating the thyroid system BUMedicine
Since a positive energy balance does not inhibit the HPT axis, the direct action of AgRP/NPY neurons must be regulating the HPT axis through suppression of TRH neurons.
Since fasting activates AgRP/NPY neurons, we wanted to determine if inhibiting their activation during fasting would prevent the fall in TH levels seen during a fast by blocking their downstream effects on TRH neurons. Indeed, our results confirm this hypothesis, showing that inhibition of ARC AgRP/NPY neurons disrupts the normal response to fasting, preventing HPT axis suppression.
However, it is still not clear why PVN TRH neurons do not respond to the low TH levels seen in fasting as the presumption has always been that all hypophysiotropic TRH neurons express MC4R, NPY receptors, and the TRβ and thus should respond to all signals. Indeed, it is reasonable to propose that TRH neurons integrate this multitude of inputs, initiating a metabolic response through the regulation of the HPT axis. To test this, we aimed to disrupt TH signaling in melanocortin-responsive neurons.
In summary, the present work shows a direct relationship between an ARC-PVN circuitry using chemogenetic techniques, and this circuitry is directly responsible for the HPT adaptive response to negative energy balance. Indeed, fasting-induced HPT axis suppression requires inhibition of TRH neurons and that is mediated, at least in part, through ARC AgRP/NPY neurons.
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