The effect of a newly developed growth hormone (GH)-releasing hexapeptide (KP-102) on GH secretion was studied in urethan-anesthetized adult male rats. Although KP-102 alone exerted a small influence on GH secretion, it produced a large plasma GH response in the presence of exogenous GH-releasing factor (GRF). During the continuous infusion of GRF, the somatotropes became refractory to a large bolus dose of GRF, but KP-102 induced a marked increase of plasma GH. The GH response to KP-102 alone or KP-102 with GRF was significantly augmented when antiserum to somatostatin (ASS) was previously administered. Although KP-102 and GRF acted synergistically on GH secretion in control animals, they acted additively in ASS-administered rats. The KP-102 effect on plasma GH was significantly attenuated in control animals and ASS-administered rats by prior i.v. injection of antiserum to GRF. Taken together, KP-102 stimulates GH secretion dependent on GRF and appears to act synergistically with GRF by antagonizing the SS effect.
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