RGD Reference Report - Combined inhibition of aromatase activity and dihydrotestosterone supplementation attenuates renal injury in male streptozotocin (STZ)-induced diabetic rats. - Rat Genome Database

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Combined inhibition of aromatase activity and dihydrotestosterone supplementation attenuates renal injury in male streptozotocin (STZ)-induced diabetic rats.

Authors: Manigrasso, MB  Sawyer, RT  Hutchens ZM, JR  Flynn, ER  Maric-Bilkan, C 
Citation: Manigrasso MB, etal., Am J Physiol Renal Physiol. 2012 May 1;302(9):F1203-9. doi: 10.1152/ajprenal.00569.2011. Epub 2012 Feb 1.
RGD ID: 7257708
Pubmed: PMID:22301628   (View Abstract at PubMed)
PMCID: PMC3362176   (View Article at PubMed Central)
DOI: DOI:10.1152/ajprenal.00569.2011   (Journal Full-text)

Our previous studies showed that streptozotocin (STZ)-induced diabetic male rats have increased estradiol and decreased testosterone levels that correlate with renal injury (Xu Q, Wells CC, Garman GH, Asico L, Escano CS, Maric C. Hypertension 51: 1218-1224, 2008). We further showed that either supplementing dihydrotestosterone (DHT) or inhibiting estradiol biosynthesis in these diabetic rats was only partially renoprotective (Manigrasso MB, Sawyer RT, Marbury DC, Flynn ER, Maric C. Am J Physiol Renal Physiol 301: F634-F640, 2011; Xu Q, Prabhu A, Xu S, Manigrassso MB, Maric C. Am J Physiol 297: F307-F315, 2009). The aim of this study was to test the hypothesis that the combined therapy of DHT supplementation and inhibition of estradiol synthesis would afford better renoprotection than either treatment alone. The study was performed in 12-wk-old male nondiabetic (ND), STZ-induced diabetic (D), and STZ-induced diabetic rats that received the combined therapy of 0.75 mg/day of DHT along with 0.15 mg . kg(-1) . day(-1) of an aromatase inhibitor, anastrozole (Dta), for 12 wk. Treatment with the combined therapy resulted in attenuation of albuminuria by 84%, glomerulosclerosis by 55%, and tubulointerstitial fibrosis by 62%. In addition, the combined treatment decreased the density of renal cortical CD68-positive cells by 70% and decreased protein expression of transforming growth factor-beta protein expression by 60%, collagen type IV by 65%, TNF-alpha by 55%, and IL-6 by 60%. We conclude that the combined treatment of DHT and blocking aromatase activity in diabetic male STZ-induced diabetic rats provides superior treatment than either treatment alone in the prevention of diabetic renal disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diabetic Nephropathies treatmentISOCyp19a1 (Rattus norvegicus)7257708; 7257708associated with Diabetes Mellitus and ExperimentalRGD 
Diabetic Nephropathies treatmentIMP 7257708associated with Diabetes Mellitus and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp19a1  (cytochrome P450, family 19, subfamily a, polypeptide 1)

Genes (Mus musculus)
Cyp19a1  (cytochrome P450, family 19, subfamily a, polypeptide 1)

Genes (Homo sapiens)
CYP19A1  (cytochrome P450 family 19 subfamily A member 1)


Additional Information