Thyrotropin-releasing hormone (TRH) blocks glucagon-induced hyperglycemia in mice: dissociation of the antihyperglycemic and pituitary actions of TRH.

Thyrotropin-releasing hormone (TRH) prevents the development of drug- or stress-induced hyperglycemia in mice through action at central sites. To study the role of the pituitary in mediating this action, we have evaluated the effect of TRH analogs lacking hypophysiotropic activity, acid-TRH and DN 1417, in blocking glucagon-induced hyperglycemia in mice. In addition, the effect of hypophysectomy on TRH antihyperglycemic action was examined. It was found that central injection of acid-TRH or DN 1417 (0.1-10 micrograms) fully mimics TRH in blocking glucagon (5 micrograms)-stimulated hyperglycemia. Moreover, TRH (1 or 10 micrograms) was fully active in blocking glucagon-induced hyperglycemia in hypophysectomized mice. These results exclude the possibility that pituitary factors play a role in the central antihyperglycemic action of TRH.