The effects of the TRH metabolite cyclo(His-Pro) and its analogs on feeding

Cyclo(His-Pro), or cHP, is a putative metabolite of thyrotropin-releasing hormone (TRH), and, like TRH, can inhibit food intake but requires higher doses. In attempts to improve the anorectic effects of cHP through modification of its structure, a number of its analogs were synthesized. These analogs or cHP itself were administered to rats either by intracerebroventricular (ICV) infusion or systemic injection, and their effects on food intake were measured. None of the synthetic analogs was more potent than cHP, although several analogs demonstrated comparable potencies to the parent compound. Interestingly, one cHP analog reversed the suppressive effect and stimulated feeding. This reversal, as well as the preservation of the anorectic effect by some but not all the analogs, suggests that the cHP effect on feeding does require specific structural features.