Synthetic hGH causes both increased somatomedin levels and insulin resistance in humans

The supply of human pituitary growth hormone (hGH) available has been limited by the number of donors. Recently, methionyl-hGH (Genentech) has been synthesized by recombinant DNA techniques. We have compared synthetic methionyl-hGH with pituitary hGH in twelve normal adult male volunteers. Each patient was given 4 daily doses of 16 U of each hGH with a 10 day period between hGH preparations. Somatomedin-C (SM-C) by RIA was determined daily. Glucose tolerance tests were done prior to the first and after the fourth injection. The SM-C by RIA increased from a baseline of 1.04 ± 0.07 U/ml to 2.95 ± 0.20 U/ml with methionyl-hGH and from 1.11 ±0.06 U/ml to 3.08 ± 0.19 U/ml with pituitary hGH. The GTT glucose area increased from 348 ± 16 mg%-hr to 475 ± 30 mg%-hr and the insulin area increased from 133 ± 19 uU/ml-hr to 403 ± 55 uU/ml-hr with methionyl-hGH. The glucose area increased from 333 ± 14 mg%-hr to 435 ± 25 mg%-hr and the insulin area increased from 110 ± 12 uU/ml-hr to 324 ± 49 uU/ml-hr with pituitary hGH. The equal somatomedin responses are evidence that the synthetic methionyl hGH has full biological activity. The equal changes in glucose metabolism demonstrate that insulin resistence is linked to monocomponent synthetic hGH as well as pituitary hGH. These studies open the way for explorations of uses of methionyl-hGH in human disease states and developmental disorders.