Testosterone treatment promotes tubular damage in experimental diabetes in prepubertal rats.
Puberty unmasks or accelerates progressive kidney diseases, including diabetes mellitus (DM), perhaps through effects of sex steroids. To test the hypothesis that rising androgen levels at puberty permit diabetic kidney damage, we studied four groups of male rats with and without streptozocin-induced DM: adult onset (A), adult onset after castration (AC), juvenile onset (J), and juvenile onset with testosterone treatment (JT). Profibrotic markers were measured after 6 wk with blood glucose levels 300-450 mg/dl. JT permitted increased expression of mRNA for two isoforms of transforming growth factor-beta and connective tissue growth factor compared with J animals with DM; prior castration did not provide protection in adult-onset DM. JT also permitted greater tubular staining for alpha-smooth muscle actin and fibroblast-specific protein, two markers of cell damage and potential epithelial mesenchymal transition. Once again, castration was not protective for these effects of DM in the AC group. These data indicate that puberty permits detrimental effects in the tubulointerstitium in the diabetic kidney, an effect mimicked by testosterone treatment of juvenile animals and partially blunted by castration of adults, but damage does not correlate with testosterone levels, suggesting a less direct mechanism.
Sun
Jianhong
J
Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198-2169, USA.
Devish
Kay
K
Langer
William J
WJ
Carmines
Pamela K
PK
Lane
Pascale H
PH
D000818:Animals; D055513:Connective Tissue Growth Factor; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000473:pathology*; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology*; D007686:Kidney Tubules, Distal / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation; D013739:Testosterone / Q000633:toxicity*; D016707:Tissue Fixation; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000097:blood / Q000652:urine; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis / Q000097:blood / Q000652:urine; D053782:Transforming Growth Factor beta3 / Q000096:biosynthesis / Q000097:blood / Q000652:urine
C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D055513:Connective Tissue Growth Factor; D013739:Testosterone