title: Sex-dependent differences in renal angiotensinogen as an early marker of diabetic nephropathy.
abstract: OBJECTIVE
  The renal renin-angiotensin system (RAS) has been implicated in the pathogenesis of diabetic nephropathy. The aim of this study was to investigate sex differences in renal renin-angiotensin system (RAS) and the roles of androgens in diabetes-associated renal injury.
  
  
  METHODS
  Renal injury and fibrosis were studied in streptozotocin-induced diabetic rats by albuminuria and by gene expression of collagen I and fibronectin. RAS was investigated by analysing the plasma angiotensinogen (AOGEN) and renin activity (PRA) and their renal gene expression. Also, a group of diabetic rats was treated with the anti-androgen flutamide.
  
  
  RESULTS
  Albuminuria was significantly lower in diabetic females than in males (1.2 [0.8-1.5] versus 4.4 [2.2-6.1] mg/24 h, data are median [IQR] values, P < 0.05). Renal AOGEN mRNA levels were increased by diabetes in males (8.1 ± 0.8% in diabetes versus 0.8 ± 0.2% in control, P < 0.001) but not in females (1.0 ± 0.1% in diabetes versus 0.8 ± 0.1% in control, P > 0.05), as were collagen I and fibronectin mRNAs. Furthermore, AOGEN mRNA levels were strongly correlated with albuminuria (Spearman r = 0.64, 95% [CI] 0.36-0.81, P < 0.0001). Diabetes decreased PRA, renal renin mRNA and plasma AOGEN in both females and males. Anti-androgen treatment decreased albuminuria only in diabetic males without affecting the endocrine or renal RAS.
  
  
  CONCLUSIONS
  These data indicate that renal but not hepatic AOGEN or renin is positively associated with diabetic albuminuria and contribute to the sex-dependent differences in renal injury. Androgens may contribute to albuminuria in male independently of the RAS.
authors.affiliation: Center of Innovation, Technology and Education-(CITE), University Camilo Castelo Branco, Sao Jose dos Campos, Brazil.
authors.forename: D
authors.initials: D
authors.lastname: de Alencar Franco Costa
authors.forename: M
authors.initials: M
authors.lastname: Todiras
authors.forename: L A
authors.initials: LA
authors.lastname: Campos
authors.forename: J
authors.initials: J
authors.lastname: Cipolla-Neto
authors.forename: M
authors.initials: M
authors.lastname: Bader
authors.forename: O C
authors.initials: OC
authors.lastname: Baltatu
mesh_terms: D000419:Albuminuria / Q000097:blood / Q000209:etiology; D000726:Androgen Antagonists / Q000494:pharmacology; D000808:Angiotensinogen / Q000097:blood* / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000097:blood; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D005485:Flutamide / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D000726:Androgen Antagonists; D015415:Biomarkers; D024042:Collagen Type I; D005353:Fibronectins; D012333:RNA, Messenger; D000808:Angiotensinogen; D005485:Flutamide; D012083:Renin
keywords: albuminuria; androgens; diabetes; renal angiotensinogen; sexual dimorphism