Reduced and S-carboxymethylated human growth hormone: a probe for diabetogenic action

Abstract
The biological activity profile of reduced and S-carboxymethylated human growth hormone (RCM-hGH) was determined to establish its suitability for study of the diabetogenic property of hGH. RCM-hGH has greatly attenuated in vivo growth-promoting activity in the 9-day weight gain test in hypophysectomized rats (.apprx. 1%) and to have a similar low order of in vitro activity in stimulating amino acid incorporation into the protein of the isolated rat diaphragm. RCM-hGH also only had .apprx. 1% of the in vitro insulin-like activity of the native hormone on isolated adipose tissue from hypophysectomized rats. In contrast, RCM-hGH retained sustantial in vivo diabetogenic activity in the ob/ob mouse, appearing to have .apprx. 50% of the activity of the native hormone. RCM-hGH was also found to retain significant, although attenuated (25%), in vitro lactogenic activity when tested for the ability to stimulate amino acid incorporation into a casein-rich protein fraction in mouse mammary gland explants. Because RCM-hGH exhibits a high degree of diabetogenic activity, although lacking significant anabolic or insulin-like activities, it will be useful as a monovalent probe for the study of the molecular mechanism of the diabetogenic action of GH.