Growth hormone specifically stimulates the expression of low density lipoprotein receptors in human hepatoma cells.
Human GH (hGH) has been shown to stimulate hepatic low density lipoprotein (LDL) receptor expression in man in vivo. To further characterize this effect in vitro, we determined the expression of LDL receptors in cultured human hepatoma (HepG2) cells exposed to hGH. After incubation with hGH, stimulation of LDL receptors appeared at a concentration of 0.25 nM hGH. The presence of hGH receptors on HepG2 cells could be demonstrated by immunocytochemistry using a hGH receptor-specific monoclonal antibody. Binding studies, using 125I-labeled hGH, revealed high affinity binding with the appropriate somatogenic specificity. The LDL receptor induction was specific for hGH, as both bovine GH and recombinant human PRL were without effect. The LDL receptor stimulation occurred in parallel with increased levels of LDL receptor messenger RNA. Inclusion of dexamethasone and thyroid hormone in the incubation medium enhanced the LDL receptor stimulation by hGH. Although incubation with insulin-like growth factor-I (IGF-I) stimulated LDL receptor expression, the hGH-induced stimulation was unaltered after preincubation of cells with a monoclonal mouse anti-IGF-I antibody, suggesting that the release of IGF-I is not involved in LDL receptor stimulation by hGH. We conclude that hGH specifically induces the LDL receptor in cultured HepG2 cells at both the protein and the messenger RNA level, and that the induction is independent of IGF-I release.
Parini
P
P
Department of Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Angelin
B
B
Lobie
P E
PE
Norstedt
G
G
Rudling
M
M
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics; D013963:Thyroid Hormones / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D011973:Receptors, LDL; D013963:Thyroid Hormones; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D013006:Growth Hormone