Receptor binding properties and insulin-like effects of human growth hormone and its 20 kDa-variant in rat adipocytes.
The natural 20 kDa-variant of human growth hormone (hGH) binds with high affinity to IM-9 human lymphocyte receptors, in agreement with its potency in biological assays for growth promoting and lactogenic activities. In contrast, 20 kDa-hGH has only 3% of the potency of 22 kDa-hGH in binding to the receptors of normal and hypophysectomized rat adipocytes. In agreement with the binding potency, 20 kDa-hGH is only 3% as potent as 22 kDa-hGH in stimulating lipogenesis in normal rat adipocytes preincubated for a few hours in hGH-free medium. The 20 kDa-hGH is also much weaker than 22 kDa-hGH in stimulating lipogenesis in adipocytes from hypophysectomized rats. These data strongly support the concept that the rat adipocyte receptor, which mediates the insulin-like effects of growth hormone, is different from the receptor found on human IM-9 lymphocytes. Preincubation of rat adipocytes with hGH induces a refractoriness to subsequent activation of lipogenesis by hGH but does not abolish the response to insulin, while preincubation with insulin slightly potentiates the hGH response and does not change the insulin response. Additivity studies and a detailed comparison of the lipogenic effects of insulin and hGH suggest that hGH shares only a subset of the metabolic pathways activated by insulin.
Smal
J
J
Closset
J
J
Hennen
G
G
De Meyts
P
P
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D013006:Growth Hormone / Q000378:metabolism* / Q000494:pharmacology; D019382:Human Growth Hormone; D006801:Humans; D007016:Hypophysectomy; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011986:Receptors, Somatotropin / Q000378:metabolism*
D007328:Insulin; D008055:Lipids; D010446:Peptide Fragments; D011986:Receptors, Somatotropin; C039519:somatotropin 20K; D019382:Human Growth Hormone; D013006:Growth Hormone