Impairment of renal steroidogenesis at the onset of diabetes

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:524

Article

Pagotto, Melina A.¹  Roldan, Maria L.²  Molinas, Sara M.^2,3  Raices, Trinidad⁴  Pisani, Gerardo B.⁵  Pignataro, Omar P.^4,6  Monasterolo, Liliana A.^2,3,7 

[1] Natl Sci & Tech Res Council IFISE CONICET, Inst Expt Physiol, Suipacha 531, RA-2000 Rosario, Argentina

[2] Natl Univ Rosario, Fac Biochem & Pharmaceut Sci, Pharmacol, Suipacha 531, RA-2000 Rosario, Argentina

[3] Natl Sci & Tech Res Council CONICET, Buenos Aires, DF, Argentina

[4] Natl Sci & Tech Res Council CONICET, Lab Mol Endocrinol & Signal Transduct, Inst Biol & Expt Med IBYME, C1428ADN, Buenos Aires, DF, Argentina

[5] Natl Univ Rosario, Fac Biochem & Pharmaceut Sci, Morphol, Suipacha 531, RA-2000 Rosario, Argentina

[6] Univ Buenos Aires UBA, Sch Sci, Dept Biol Chem, RA-1428 Buenos Aires, DF, Argentina

[7] Natl Univ Rosario CIC UNR, Res Council, Rosario, Santa Fe, Argentina

关键词: Kidney;    Steroidogenesis;    Diabetes;    CYP11A1;    StAR;    Pregnenolone;   

DOI  :  10.1016/j.mce.2021.111170

来源: Elsevier

【 摘 要 】

Accumulating evidence indicates the association between changes in circulating sex steroid hormone levels and the development of diabetic nephropathy. However, the renal synthesis of steroid hormones during diabetes is essentially unknown. Male Wistar rats were injected with streptozotocin (STZ) or vehicle. After one week, no changes in functional or structural parameters related to kidney damage were observed in STZ group; however, a higher renal expression of proinflammatory cytokines and HSP70 was found. Expression of Steroidogenic Acute Regulatory protein (StAR) and P450scc (CYP11A1) was decreased in STZ kidneys. Incubation of isolated mitochondria with 22R-hydroxycholesterol revealed a marked inhibition in CYP11A1 function at the medullary level in STZ group. The inhibition of these first steps of renal steroidogenesis in early STZ-induced diabetes led to a decreased local synthesis of pregnenolone and progesterone. These findings stimulate investigation of the probable role of nephrosteroids in kidney damage associated with diabetes.

【 授权许可】

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