Effect of Tyr-Pro-Leu-Gly-NH2 on melanotropin-stimulating hormone release in the frog and rat.

The tetrapeptide Tyr-Pro-Leu-Gly-NH2 (Tyr-MIFI) has been recently characterized in the hypothalamus and pineal of the rat. Since the concentration of Tyr-MIFI in the brain is increased by pinealectomy and is higher when the animals are in the dark, the possibility that Tyr-MIFI could be a physiological regulator of melanotropin secretion has been investigated. For this study a well-defined perifusion model has been applied, using whole neurointermediate lobes from male frogs (Rana ridibunda Pallas) or male Wistar rats. The amount of alpha-MSH released in the effluent perifusate was measured by means of a sensitive and specific radioimmunoassay method. For concentrations ranging from 10(-10) to 10(-6) M, Tyr-MIFI did not significantly alter the spontaneous release of alpha-MSH in the frog nor did it alter the release of alpha-MSH in the rat. Since it has been recently demonstrated that the tripeptide pGlu-His-Pro-NH2 (mammalian TRH) is a specific MSH-releasing factor in the frog, the possibility that Tyr-MIFI could modulate the response of the intermediate lobe of the frog to TRH has also been investigated. No alteration of TRH-induced alpha-MSH release was observed in the presence of a 100-fold excess of Tyr-MIFI. In addition, Tyr-MIFI was found to be unable to lighten the skin of the frog (Rana pipiens) when applied directly to the pituitary of the darkened animals. Thus these results definitively rule out the possibility that Tyr-MIFI is the melanotropin-release inhibiting factor in the frog or rat.