Growth hormone increases low-density lipoprotein receptor and HMG-CoA reductase mRNA expression in mesangial cells.
A dysregulation of the negative feedback mechanism of the low-density lipoprotein receptor (LDL-r) induced by hormones and cytokines may contribute to the development of glomerular injury and specifically could underlie growth hormone (GH)-induced glomerulosclerosis. The present study investigates the role of GH in the regulation of LDL-r and HMG-CoA reductase mRNA expression in mesangial cells. Mouse mesangial cells were equilibrated in a medium containing 5% lipoprotein-deprived serum (LPDS) for 48 h, prior to addition of GH (0.25 microM). Transcript levels of LDL-r, HMG-CoA reductase and GH-receptor (GH-r) were measured at days 2 and 4 and intracellular lipid content was evaluated by oil red-O staining. The addition of GH significantly increased both the LDL-r and HMG-CoA reductase transcript levels at day 2 compared to control. Oil red-O positive staining increased following the initial period of 48 h lipoprotein deprivation, but addition of GH in a subsequent 48-hour period did not alter lipid content to a measurable degree compared with control. The present study demonstrates that GH significantly increased HMG-CoA reductase and LDL-r transcript levels in mesangial cells deprived of lipoproteins suggesting that abnormal levels of GH may play a role in glomerular lipid accumulation.
Machado
Marcos O
MO
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Hirata
Rosario D C
RD
Hirata
Mario H
MH
Hirszel
Przemyslaw
P
Sellitti
Donald F
DF
Doi
Sonia Q
SQ
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D013006:Growth Hormone / Q000494:pharmacology / Q000502:physiology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis*; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D012333:RNA, Messenger; D011973:Receptors, LDL; D013006:Growth Hormone; D006903:Hydroxymethylglutaryl CoA Reductases