EFFECT OF CHRONIC ADMINISTRATION OF A NEW POTENT AGONIST OF GH-RH(1-29)NH2 ON LINEAR GROWTH AND GH RESPONSIVENESS IN RATS

The effects of a repeated or continuous administration of a potent ago nistic analog of growth hormone-releasing hormone (GH-RH), [Dat(1), Th r(8), Orn(12,21), Abu(15), Nle(27), Asp(28), ASm(29)] hGH-RH(1-29) (JI -36), on the linear growth and the CH responses to bolus injections of GH-RH(1-29)NH2 were investigated in male rats about 7 weeks old. Body weight and tail length were monitored. Basal serum GH and IGF-I conce ntrations and GH responses to GH-RH(1-29)NH2 were measured by RIA. Chr onic administration of GH-RH agonist JI-36 by continuous release from osmotic minipumps at the rate of 0.2 mu g/h or twice daily injections of 0.5 and 5 mu g/rat for 4 weeks significantly speeded up the growth of rats as measured by the tail length. The acceleration of growth was similar in the 3 groups and was associated with stimulation of IGF-I secretion. The GH response to bolus injection of GH-RH(1-29)NH2 was pr eserved in all groups and no attentuation of the response occurred in rats treated for 4 weeks with agonist JI-36 as compared with the contr ol group. Our results indicate that chronic administration of GH-RH ag onist JI-36 significantly increases the growth rate without affecting somatotroph responsiveness in rats. It is therefore likely that this c lass of GH-RH agonists may be useful clinically.