Testosterone treatment promotes tubular damage in experimental diabetes in prepubertal rats

Jianhong Sun, Kay Devish, William J. Langer, Pamela K Carmines, Pascale H. Lane

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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-β 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 α-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.

Original languageEnglish (US)
Pages (from-to)F1681-F1690
JournalAmerican Journal of Physiology - Renal Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 1 2007

Fingerprint

Castration
Testosterone
Diabetes Mellitus
Puberty
RNA Isoforms
Connective Tissue Growth Factor
Kidney
Epithelial-Mesenchymal Transition
Experimental Diabetes Mellitus
Kidney Diseases
Transforming Growth Factors
Type 2 Diabetes Mellitus
Androgens
Smooth Muscle
Blood Glucose
Actins
Fibroblasts
Steroids
Staining and Labeling
Proteins

Keywords

  • Castration
  • Connective tissue growth factor
  • Glomerulus
  • Transforming growth factor-β; epithelial mesenchymal transition

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Testosterone treatment promotes tubular damage in experimental diabetes in prepubertal rats. / Sun, Jianhong; Devish, Kay; Langer, William J.; Carmines, Pamela K; Lane, Pascale H.

In: American Journal of Physiology - Renal Physiology, Vol. 292, No. 6, 01.06.2007, p. F1681-F1690.

Research output: Contribution to journalArticle

Sun, Jianhong ; Devish, Kay ; Langer, William J. ; Carmines, Pamela K ; Lane, Pascale H. / Testosterone treatment promotes tubular damage in experimental diabetes in prepubertal rats. In: American Journal of Physiology - Renal Physiology. 2007 ; Vol. 292, No. 6. pp. F1681-F1690.
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