L-692,429, A NONPEPTIDE GROWTH-HORMONE (GH) SECRETAGOGUE, REVERSES GLUCOCORTICOID SUPPRESSION OF GH SECRETION

The reversal of glucocorticoid-induced negative nitrogen balance by GH supports a possible therapeutic role for GH treatment in patients rec eiving these catabolic steroids. A GH secretagogue might be of similar utility. However, stimulated GH secretion is generally suppressed by glucocorticoids. To test whether L-692,429, a nonpeptide mimic of GH-r eleasing peptide-6, can overcome such suppression, a double blind, pla cebo-controlled, three-period, cross-over study was performed in nine healthy young men who received 0.2 mg/kg L692,429, iv, preceded by 4 d ays of prednisolone (20 mg, orally, three times daily) or placebo, and 0.75 mg/kg L-692,429 preceded by prednisolone only. The mean (se) GH peak and area under the curve between 0-240 min after administration o f 0.2 mg/kg L-692,429 in the absence of steroid were 53.8 (7.2) mu g/L and 3481 (1005) mu g/min.L, which were reduced to 25.1 (3.4) mu g/L a nd 1342 (285) mu g/min.L (P less than or equal to 0.01) when treatment was preceded by 4 days of prednisolone. However, the suppressive infl uence of the steroid was attenuated by the high dose of L-692,429, whi ch achieved a GH peak and area under the curve between 0-240 min of 42 .6 (5.8) mu g/L and 2298 (425) mu g/min.L, respectively (P < 0.01 us. 0.2 mg/kg L-692,429 plus prednisolone). L-692,429 stimulates GH secret ion even in the setting of short term, high dose, concomitant glucocor ticoid treatment, suggesting that such compounds might provide an alte rnative means of increasing circulating GH and reversing the catabolic effects of these steroids.