Preservation of growth hormone secretion in response to growth hormone-releasing peptide-2 during prednisone therapy

Children who require long-term glucocorticoid treatment often demonstrate p oor growth. Growth hormone (GH) secretion is decreased during glucocorticoi d treatment, and this decrease may be due to a relative excess of the hypot halamic hormone somatostatin (SRIF). GH-releasing peptide-a (GHRP-2) is a G H secretagogue that acts via multiple mechanisms at multiple sites. One of its proposed mechanisms is the ability to bypass SRIF blockade of GH secret ion. We measured the ability of GHRP-2 to release GH before and during pred nisone therapy (20 mg orally three times daily for 4 days). The degree of p reservation of GH secretion and the pattern of GH release in response to GH RP-2 were compared with those observed in response to arginine, a known SRI F inhibitor. GH release in response to GHRP-2 and arginine was measured in the same eight subjects before and during prednisone therapy. Before predni sone, peak GH levels in response to arginine and GHRP-2 were 8.8 +/- 2.8 an d 80.8 +/- 21.2 mu g/L. During prednisone therapy, the peak GH level in res ponse to arginine and to GHRP-2 was 20.1 +/- 8.3 and 71.3 +/- 18.4 mu g/L, respectively. The difference in peak values before and after prednisone was not significant. The time to the peak GH level during prednisone therapy o ccurred sooner for both arginine and GHRP-2. The pattern of GH release to a rginine and to GHRP-2 was not identical, and the mean area under the curve for GH release to GHRP-2 decreased significantly with steroid treatment (P = .04), suggesting that GHRP-2 acts by mechanisms additional to the removal of SRIF inhibition. GHRP-2 elicited a 10-fold greater GH response than arg inine at baseline, and the GH response was threefold greater versus arginin e even in the face of prednisone therapy. GH release occurred earlier for b oth arginine and GHRP-2 during steroid treatment. We propose that this may suggest an increased storage phenomenon due to the blockade of GH secretion by glucocorticoids and then a sudden release with SRIF inhibition. If GHRP -2 can indeed counteract the inhibitory effect of glucocorticoids on GH sec retion, then a new form of therapy may be available to support growth in ch ildren who must receive long-term steroid treatment. Copyright (C) 1999 by W.B. Saunders Company.