Beneficial Effects of Estrogens on Indices of Renal Damage in Uninephrectomized SHRsp Rats

Marie Luise Gross, Marcin Adamczak, Thomas Rabe, Nevin Ali Harbi, Jan Krtil, Andreas Koch, Peter Hamar, Kerstin Amann, Eberhard Ritz

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Abstract

Renal diseases tend to be less severe among premenopausal female patients, compared with male patients. Experimental data on the effects of estrogens on renal damage are controversial, and potential underlying mechanisms have not been fully clarified. Three-month-old, female, uninephrectomized (UNX), sham-operated or ovariectomized (OVX) SHRsp rats were left untreated or received either 17β-estradiol 3-benzoate (25 μg/d) or estriol (0.02 mg/d) daily. After 3 mo, indices of renal damage (glomerulosclerosis index and tubulointerstitial damage index) and glomerular geometric parameters were investigated. The expression of desmin, TGF-β, endothelin-1, collagen IV, endothelial nitric oxide synthase, and estrogen receptors α and β in the glomeruli and tubulointerstitium was immunohistochemically evaluated. Estradiol and estriol did not significantly affect kidney weights or BP. Estradiol and estriol caused significant reductions in albuminuria (vehicle-treated UNX/OVX animals, 25.4 ± 8.52 mg/24 h; estradiol-treated UNX/OVX animals, 15.37 ± 6.12 mg/24 h; estriol-treated UNX/OVX animals, 6.54 ± 2.24 mg/24 h). The glomerulosclerosis index was significantly lower in estriol- and estradiol-treated animals (estradiol-treated UNX/OVX animals, 0.69 ± 0.16; estriol-treated UNX/OVX animals, 0.21 ± 0.12; P < 0.05), compared with vehicle-treated animals (1.46 ± 0.09); the tubulointerstitial damage index exhibited a similar pattern. The mean glomerular volume was significantly less in estrogen-treated animals. UNX/OVX animals demonstrated significantly greater expression of TGF-β and endothelin-1 in immunohistochemical, in situ hybridization, and reverse transcription-PCR assays. This increase was abrogated by estriol but not estradiol. Similarly, significantly higher glomerular and tubulointerstitial expression of proliferating cell nuclear antigen and collagen IV was observed in UNX/OVX animals, and expression was decreased by estriol but not estradiol. It was concluded that, in the UNX model of spontaneous renal damage, glomerular lesions and glomerular hypertrophy were reduced by estriol but less consistently by estradiol. In parallel, loss of podocytes, evidence of podocyte injury (i.e., desmin expression), and expression of mediator systems of glomerular damage were decreased, pointing to a major renoprotective action of estriol.

Original languageEnglish
Pages (from-to)348-358
Number of pages11
JournalJournal of the American Society of Nephrology
Volume15
Issue number2
DOIs
Publication statusPublished - Feb 1 2004

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ASJC Scopus subject areas

  • Nephrology

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