title: Growth hormone promotes glomerular lipid accumulation in bGH mice.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Uniformed Services University, Bethesda, MD 20814, USA.
authors.forename: Marcos O
authors.initials: MO
authors.lastname: Machado
authors.forename: Rosario D C
authors.initials: RD
authors.lastname: Hirata
authors.forename: Donald F
authors.initials: DF
authors.lastname: Sellitti
authors.forename: Roberto
authors.initials: R
authors.lastname: Iotti
authors.forename: Alejandro
authors.initials: A
authors.lastname: Iotti
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cusumano
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Riordan
authors.forename: Karen T
authors.initials: KT
authors.lastname: Coschigano
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.forename: Irina
authors.initials: I
authors.lastname: Zuhl
authors.forename: Nga
authors.initials: N
authors.lastname: Nguyen
authors.forename: Mario H
authors.initials: MH
authors.lastname: Hirata
authors.forename: Sonia Q
authors.initials: SQ
authors.lastname: Doi
mesh_terms: D000818:Animals; D002417:Cattle; D005838:Genotype; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000378:metabolism*; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011973:Receptors, LDL; D051116:Receptors, Scavenger; D013006:Growth Hormone