title: Progesterone ameliorates diabetic nephropathy in streptozotocin-induced diabetic Rats.
abstract: BACKGROUND
  Previous studies reported that 17β-estradiol may influence the progression of diabetic renal disease in females. The present study was intended to provide an insight into the specific effects of progesterone, the other female sex hormone, in the diabetic renal complications.
  
  
  METHODS
  Adult female wistar rats were divided into four groups (n = 6/group): intact control (non-diabetic, ND), intact diabetic (D), ovariectomized diabetic (D-OVX) and ovariectomized diabetic which were treated with progesterone (D-OVX + P; 10 mg/kg, s.c, every second day) for 10 weeks. Diabetes was induced by a single dose injection of 55 mg/kg streptozotocin. Expressions of transforming growth factor-β (TGF-β), fibronectin, vascular endothelial growth factor-A (VEGF-A), angiotensin II type 1 receptor (ATR1) and podocyte markers (nephrin and podocin) were assessed by immunohistochemistry and real-time PCR.
  
  
  RESULTS
  The treatment of D-OVX rats with progesterone attenuated diabetic-associated increases in the urinary albumin to creatinine ratio, glomerulosclerosi and the expression of profibrotic and angiogenic factors (TGF-β, Fibronectin and VEGF-A). Furthermore, progesterone supplementation prevented diabetes-induced downregulation of nephrin and podocin while the overexpression of ATR1 in the diabetic rats was inhibited by the progesterone supplementation.
  
  
  CONCLUSIONS
  These results provided evidence, for the first time, that the replacement of progesterone can ameliorate the renal damage in the experimental models of diabetic nephropathy through improving the renal function; the inhibition of renal fibrosis and abnormal angiogenesis; along with the amelioration of podocyte injury. Additionally, the blocking of renin-angiotensin system through the down-regulation of ATR1 expression may also account for the reno-protective effect of progesterone.
authors.affiliation: Department of Biological Sciences, Yarmouk University, Irbid, Jordan ; Department of Physiology, College of Medicine, University of Ha'il, 2440 Hail, Saudi Arabia.
authors.forename: Bahaa
authors.initials: B
authors.lastname: Al-Trad
authors.affiliation: Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Ha'il, Ha'il, Saudi Arabia ; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ibraheem M
authors.initials: IM
authors.lastname: Ashankyty
authors.affiliation: Department of Pharmacology, College of Medicine, University of Ha'il, Hail, Saudi Arabia.
authors.forename: Mohd
authors.initials: M
authors.lastname: Alaraj
keywords: Angiogenesis; Angiotensin II type 1 receptor; Diabetic nephropathy; Fibrosis; Progesterone