Growth hormone regulation of lipid metabolism in cells transfected with growth hormone receptor cDNA.
The functional properties of the growth hormone (GH) receptor was studied using cellular transfection of GH receptor cDNA. GH treatment (1.5-2 h) of Chinese hamster ovary cells, stably transfected with GH receptor cDNA (CHO4), resulted in increased cellular lipid synthesis (240% of control). This effect was blocked by staurosporine, suggesting a dependence on cellular kinases. However, if GH treatment of CHO4 cells was prolonged (16 h), this instead stimulated lipolysis (128% of control). The GH receptor in CHO4 cells was also shown to be functional in terms of ligand internalization. A GH receptor mutant, in which 183 amino acids had been deleted in the carboxyterminal of the intracellular domain was functionally active, while a receptor without its intracellular domain was shown to be inactive. In conclusion, GH receptors expressed in CHO cells are functional and GH was also shown to have both an acute insulin-like effect, which was kinase dependent, and a long-term anti-insulin-like effect on the lipid metabolism. This suggests that an approach using GH receptor cDNA transfected cells can be of value in understanding the mechanism of GH action.
Möller
C
C
Center for Biotechnology, Karolinska Institute, Huddinge, Sweden.
Emtner
M
M
Arner
P
P
Norstedt
G
G
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D013006:Growth Hormone / Q000494:pharmacology*; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011986:Receptors, Somatotropin / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D019311:Staurosporine; D013997:Time Factors; D014162:Transfection
D000470:Alkaloids; D011986:Receptors, Somatotropin; D011993:Recombinant Fusion Proteins; D013006:Growth Hormone; D011493:Protein Kinase C; D019311:Staurosporine