Retention of Biologic Activity of Human Growth Hormone in Man After Reduction and Alkylation

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Abstract
This study demonstrates the lipolytic, nitrogen-retaining, calciuric and insulinotropic capacities of reduced tetra-S-carbamidomethyl hGH (RCAM-hGH). hGH was reduced with dithiothreitol and alkylated with iodoacetamide to yield RCAM-hGH. Total reduction was confirmed by quantitative yield of 4 residues of S-carboxymethylcysteine per mole RCAM-hGH. After 8 days on a diet of known composition, 2 prepubertal males with growth hormone deficiency received 5 mg RCAM-hGH im daily for 5 to 6 days. Five to 7 days later, 5 mg hGH im daily, was given for 4 days. RCAM-hGH administration caused an average daily decrease in urinary nitrogen of 39% and increased urinary calcium to 150% of control value. The rise in plasma free fatty acids 4 hr after im injection of RCAM-hGH or of hGH was similar. Intravenous glucose disposal (Kg 1.55) on the 4th day of RCAM-hGH administration was unchanged from the control value. Fasting insulin (IRI) increased from 6 to 21 μU/ml and the area of IRI response to glucose rose to 250% above control value following administration of RCAM-hGH. Despite previously demonstrated immunologic differences, the qualitative and quantitative biological activity of RCAM-hGH and native hGH was similar.

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