Reduced and S-carboxymethylated human growth hormone: a probe for diabetogenic action.
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 was found to have greatly attenuated in vivo growth-promoting activity in the 9-day weight-gain test in hypophysectomized rats (approximately 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 approximately 1% of the in vitro insulin-like activity of the native hormone on isolated adipose tissue from hypophysectomized rats. In contrast, RCM-hGH retained substantial in vivo diabetogenic activity in the ob/ob mouse, appearing to have approximately 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.
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced*; D003964:Diaphragm / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects; D051379:Mice; D008820:Mice, Obese; D011247:Pregnancy; D051381:Rats; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D001786:Blood Glucose; C043442:S-carboxymethylsomatotropin; D013006:Growth Hormone; D007930:Leucine