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.