Growth hormone promotes glomerular lipid accumulation in bGH mice.

BACKGROUND: Bovine growth hormone (bGH) transgenic mice develop progressive glomerulosclerosis and exhibit abnormalities in hepatic lipid metabolism. We have previously shown that growth hormone up-regulates the low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) in mouse mesangial cells. However, a role of lipid abnormalities in bGH kidney disease has not yet been demonstrated.
METHODS: Groups of bGH mice (5 and 11 months old) presenting with, respectively, moderate and severe degrees of glomerulosclerosis were compared to age-matched controls. Neutral lipid content in kidney cortex was determined by oil red-O staining, serum cholesterol, and triglycerides by enzymatic assays, relative mRNA expression of LDL receptors, HMGR, and scavenger receptor by real-time reverse transcription-polymerase chain reaction (RT-PCR), and HMGR protein expression by immunoblotting. Two younger (5 and 12 weeks old) groups of mice were used to study scavenger receptor expression at earlier time points.
RESULTS: Serum cholesterol was significantly increased in bGH mice at 5 months, but triglycerides were lower than control levels at both 5 and 11 months. Renal cortex HMGR expression was elevated at the mRNA but not at the protein level in the 11-month-old bGH group compared to controls. However, glomerular neutral lipid staining and scavenger receptor mRNA expression were markedly increased in all bGH mice, including those at 5 weeks of age compared to respective controls.
CONCLUSION: The bGH mouse exhibits an increased mesangial lipid content and elevated scavenger receptor mRNA expression as early as at 5 weeks of age, suggesting that an increased kidney uptake of oxidized LDL could play a role in the development of glomerulosclerosis in this mouse model.