Growth hormone restores hepatic lipase mRNA levels but the translation is impaired in hepatocytes of hypothyroid rats.
During hypothyroidism, hepatic lipase (HL) activity is decreased. The low HL may be due to thyroid hormone insufficiency or to the concomitant fall in growth hormone (GH) activity. We studied HL expression in hepatocytes freshly isolated from hypothyroid rats with and without additional GH-substitution. In all animals HL mRNA was detected by RT-PCR in the hepatocytes, but not in the non-parenchymal cells. In hypothyroid cells HL mRNA levels were reduced by 40%, and the in vitro secretion of HL-activity and HL-protein was decreased by about 50%. In cells from GH-substituted hypothyroid rats, HL mRNA level was normalised, but the secretion of HL remained low. The specific enzyme activity of secreted HL was similar under all conditions. The discrepancy between HL mRNA and HL secretion in GH-supplemented rats may be due to (post)translational effects. Therefore we studied the HL synthesis and maturation in hepatocytes from hypothyroid and GH-substituted rats. Pulse-labelling experiments with [(35)S]methionine showed that the incorporation of [(35)S]methionine into HL protein was lower both in hypothyroid cells and in GH-supplemented cells than in control cells. During the subsequent chase, the intracellular processing and transport of newly synthesized HL protein in the hepatocytes from hypothyroid rats, whether or not supplemented with GH, was similar to control cells. We conclude that in livers of hypothyroid, GH-substituted rats translation of HL mRNA is inhibited despite restoration of HL mRNA levels.
Neve
B P
BP
Department of Biochemistry, Erasmus University Rotterdam, The Netherlands.
Hoogerbrugge
N
N
Verhoeven
A J
AJ
Birkenhäger
J C
JC
Jansen
H
H
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics*; D019382:Human Growth Hormone / Q000494:pharmacology*; D007037:Hypothyroidism / Q000139:chemically induced / Q000201:enzymology*; D008049:Lipase / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008715:Methionine / Q000378:metabolism; D012313:RNA / Q000032:analysis* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012260:Ribonucleases / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013997:Time Factors
D013462:Sulfur Radioisotopes; D019382:Human Growth Hormone; D012313:RNA; D008715:Methionine; D012260:Ribonucleases; D008049:Lipase