Effect of chronic administration of a new potent agonist of GH-RH(1–29)NH 2 on linear growth and GH responsiveness in rats

Abstract

The effects of a repeated or continuous administration of a potent agonistic analog of growth hormone-releasing hormone (GH-RH), [Dat 1, Thr 8, Orn 12,21, Abu 15, Nle 27, Asp 28, Agm 29] hGH-RH(1–29) (JI-36), on the linear growth and the GH responses to bolus injections of GH-RH(1–29)NH 2 were investigated in male rats about 7 weeks old. Body weight and tail length were monitored. Basal serum GH and IGF-I concentrations and GH responses to GH-RH(1–29)NH 2 were measured by RIA. Chronic administration of GH-RH agonist JI-36 by continuous release from osmotic minipumps at the rate of 0.2 μg/h or twice daily injections of 0.5 and 5 7gmg/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)NH 2 was preserved in all groups and no attentuation of the response occurred in rats treated for 4 weeks with agonist JI-36 as compared with the control group. Our results indicate that chronic administration of GH-RH agonist JI-36 significantly increases the growth rate without affecting somatotroph responsiveness in rats. It is therefore likely that this class of GH-RH agonists may be useful clinically.