Neuropeptides TRH and cyclo(His-Pro) share neuromodulatory, but not stimulatory, action on hypothalamic neurons in vitro: implication for the regulation of feeding.

Electrical activity of neurons in rat hypothalamic ventromedial nucleus was recorded in tissue slices, to investigate central neural mechanisms underlying reduction of food intake caused by TRH and its metabolite, cyclo(His-Pro) [cHP]. Application of TRH had two actions: stimulation of neuronal activity, which was desensitized on closely repeated applications; and modulation of neuronal responses to neurotransmitters, even in the absence of the stimulatory action. The neuromodulatory but not the direct stimulatory action could also be achieved by cHP. The neuromodulatory action is more likely to be a neural mechanism underlying the inhibition of feeding, while other biological functions, unique to TRH, may depend on direct stimulation. In this way, TRH could achieve different biological results through different modes of action on hypothalamic neurons.