title: L-692,429, a nonpeptide growth hormone (GH) secretagogue, reverses glucocorticoid suppression of GH secretion.
abstract: The reversal of glucocorticoid-induced negative nitrogen balance by GH supports a possible therapeutic role for GH treatment in patients receiving 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-releasing peptide-6, can overcome such suppression, a double blind, placebo-controlled, three-period, cross-over study was performed in nine healthy young men who received 0.2 mg/kg L-692,429, i.v., preceded by 4 days 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 of 0.2 mg/kg L-692,429 in the absence of steroid were 53.8 (7.2) micrograms/L and 3481 (1005) micrograms/min.L, which were reduced to 25.1 (3.4) micrograms/L and 1342 (285) micrograms/min.L (P < or = 0.01) when treatment was preceded by 4 days of prednisolone. However, the suppressive influence of the steroid was attenuated by the high dose of L-692,429, which achieved a GH peak and area under the curve between 0-240 min of 42.6 (5.8) micrograms/L and 2298 (425) micrograms/min.L, respectively (P < 0.01 vs. 0.2 mg/kg L-692,429 plus prednisolone). L-692,429 stimulates GH secretion even in the setting of short term, high dose, concomitant glucocorticoid treatment, suggesting that such compounds might provide an alternative means of increasing circulating GH and reversing the catabolic effects of these steroids.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey 07065-0914.
authors.forename: B J
authors.initials: BJ
authors.lastname: Gertz
authors.forename: D G
authors.initials: DG
authors.lastname: Sciberras
authors.forename: L
authors.initials: L
authors.lastname: Yogendran
authors.forename: K
authors.initials: K
authors.lastname: Christie
authors.forename: K
authors.initials: K
authors.lastname: Bador
authors.forename: D
authors.initials: D
authors.lastname: Krupa
authors.forename: J M
authors.initials: JM
authors.lastname: Wittreich
authors.forename: I
authors.initials: I
authors.lastname: James
mesh_terms: D000328:Adult; D001552:Benzazepines / Q000009:adverse effects / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007700:Kinetics; D008297:Male; D011239:Prednisolone / Q000494:pharmacology; D011388:Prolactin / Q000097:blood; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D001552:Benzazepines; D005938:Glucocorticoids; D013777:Tetrazoles; C081455:L 692429; D011388:Prolactin; D013006:Growth Hormone; D011239:Prednisolone; D006854:Hydrocortisone