Opposite effects of testosterone and estrogens on chronic allograft nephropathy

Antus, Balázs; Yao, Yousheng; Song, Erwei; Liu, Shanying; Lutz, Jens; Heemann, Uwe

doi:10.1111/j.1432-2277.2002.tb00205.x

Cited by 30 publications

(20 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Muller et al (34) demonstrated that kidneys transplanted into ovariectomized, testosterone-treated females demonstrated increased interstitial fibrosis, glomerular sclerosis, proteinuria, and increased expression of fibronectin and TGF-␤1 compared with estradiol treated ovariectomized females. Similarly, Antus et al (2) found that kidneys transplanted into castrate male rats treated with testosterone exhibited increased proteinuria, profound glomerulosclerosis, and increased TGF-␤1 and platelet-derived growth factor-A and -B expression, irrespective of donor gender, compared with estradiol or vehicle-treated castrated male rats. The authors further demonstrated that the adverse effects of androgens on chronic allograft nephropathy are mediated by dihydrotestosterone, as the histologic deterioration and expression of profibrotic mediators were inhibited by treatment with both the anti-androgen flutamide and the 5 alpha-reductase inhibitor finasteride (1).…”

Section: Discussionmentioning

confidence: 99%

Testosterone exacerbates obstructive renal injury by stimulating TNF-α production and increasing proapoptotic and profibrotic signaling

Metcalfe¹,

Leslie

Campbell³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

100

View full text Add to dashboard Cite

Upper urinary tract obstruction is a common cause of renal dysfunction in children and adults. While there is clinical evidence of an increased male incidence and mortality rate with acute renal failure, the effect of gender and testosterone on obstructive renal injury has not previously been evaluated. We hypothesized that testosterone exacerbates proinflammatory TNF-␣ production and proapoptotic and profibrotic signaling during renal obstruction, resulting in increased apoptotic cell death and tubulointerstitial fibrosis. To study this, male, female, castrated male, and testosterone-treated oophorectomized female rats were subjected to sham operation or 3 days of unilateral ureteral obstruction (UUO). Renal cortical tissue was then analyzed for TNF-␣ production; proapoptotic caspase-8, -9, and -3 activity; apoptotic cell death; profibrotic transforming growth factor-␤1 production; and ␣-smooth muscle actin expression. In a separate arm, glomerular filtration rate (inulin clearance) was measured in rats pre-and post-UUO. Male and testosterone-treated oophorectomized female rats demonstrated a significant increase in TNF-␣ production, caspase activity, apoptotic cell death, tubulointerstitial fibrosis, and renal dysfunction during UUO compared with castrated males and normal female rats subjected to the same time course of obstruction. These results demonstrate that endogenous testosterone production in normal male rats and testosterone exogenously administered to oophorectomized females significantly increases TNF production and proapoptotic and profibrotic signaling during renal obstruction, resulting in increased apoptotic cell death, tubulointerstitial fibrosis, and renal dysfunction.

show abstract

Section: Discussionmentioning

confidence: 99%

Testosterone exacerbates obstructive renal injury by stimulating TNF-α production and increasing proapoptotic and profibrotic signaling

Metcalfe¹,

Leslie

Campbell³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

100

View full text Add to dashboard Cite

show abstract

“…Moreover, renoprotection by estrogen is described in other forms of renal injury, including rat models of chronic allograft nephropathy (CAN) (15,24,25), age-related glomerular damage (29), and hypertensive nephrosclerosis (30). The role of estrogen receptors in this process remains a subject of debate.…”

Section: Discussionmentioning

confidence: 99%

“…Investigations have focused on the effects of estrogen and testosterone on the intrinsic tissue tolerance of ischemia through differential expression of oxidative scavengers, HSPs, or other mediators (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Moreover, a number of reports describe sex differences in the development of chronic injury patterns in animal transplant models (15,24,25).…”

Section: Introductionmentioning

confidence: 99%

Improved renal ischemia tolerance in females influences kidney transplantation outcomes

Aufhauser¹,

Wang²,

Murken³

et al. 2016

Journal of Clinical Investigation

123

View full text Add to dashboard Cite

“…Estrogens or estrogen metabolites ameliorate renal damage in some (5) but not all (6,7) models of renal damage. The beneficial effect of estrogen was also noted in allograft nephropathy (8). Potential explanations for the discrepancies are that different pathomechanisms operate in the various animal models or that differences in the administered doses, application modalities, and types of estrogen metabolites account for the differences (9 -11).…”

mentioning

confidence: 99%

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

Gross¹,

Adamczak

Rabe

et al. 2004

Journal of the American Society of Nephrology

103

View full text Add to dashboard Cite

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 17␤-estradiol 3-benzoate (25 g/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-␤, endothelin-1, collagen IV, endothelial nitric oxide synthase, and estrogen receptors ␣ and ␤ 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 Ϯ 8.52 mg/24 h; estradiol-treated UNX/OVX animals, 15.37 Ϯ 6.12 mg/24 h; estriol-treated UNX/OVX animals, 6.54 Ϯ 2.24 mg/24 h). The glomerulosclerosis index was significantly lower in estriol-and estradiol-treated animals (estradiol-treated UNX/OVX animals, 0.69 Ϯ 0.16; estriol-treated UNX/OVX animals, 0.21 Ϯ 0.12; P Ͻ 0.05), compared with vehicle-treated animals (1.46 Ϯ 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-␤ 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.Several studies have demonstrated that the severity and rate of progression of renal diseases tend to be greater among men, compared with women (1). This is true for several types of renal diseases, such as membranous nephropathy (2), IgA nephropathy (3), and polycystic kidney disease (4). The data from experimental studies are controversial, and very few molecular data are available. Estrogens or estrogen metabolites ameliorate renal damage in some (5) but not all (6,7) models of renal damage. The beneficial effect of estrogen was also noted in allograft nephropathy (8). Potential explanations for the discrepancies are that different pathomechanisms operate in the various animal models or th...

show abstract

Opposite effects of testosterone and estrogens on chronic allograft nephropathy

Cited by 30 publications

References 41 publications

Testosterone exacerbates obstructive renal injury by stimulating TNF-α production and increasing proapoptotic and profibrotic signaling

Testosterone exacerbates obstructive renal injury by stimulating TNF-α production and increasing proapoptotic and profibrotic signaling

Improved renal ischemia tolerance in females influences kidney transplantation outcomes

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

Contact Info

Product

Resources

About