Motilin: a novel growth hormone releasing agent

Motilin, a gastrointestinal peptide recently detected in the rat brain, was capable of stimulating growth hormone (GH) release from dispersed anterior pituitary cells in a dose-related fashion. In initial experiments, the minimum effective concentration was 10(-7) M and the effect was specific for just GH. Subsequent experiments demonstrated that concentrations of synthetic motilin as low as 10(-9) M could significantly stimulate GH release. Only large IV doses (100 micrograms) of motilin significantly elevated circulating GH levels in vivo. However, administration of antiserum to porcine motilin (100 microliters, IV) significantly depressed plasma GH levels, suggesting a physiologic role for median eminence and hypothalamic motilin in the control of GH secretion. Furthermore, infusion of motilin into the third ventricle of conscious rats resulted in a significant depression of GH levels, suggesting an ultrashort loop feedback action of motilin on the release of motilin itself or somatostatin. In light of motilin's only minor structural similarity to human pancreatic tumor GH-releasing factor (GRF) and the ability of passive immunoneutralization of motilin to lower GH, this 22-amino acid peptide must now be considered a physiologic GRF.