INVESTIGADORES
MOLINAS Sara Maria
congresos y reuniones científicas
Título:
Alterations of renal steroidogenic ability and sex hormones content at an early stage of experimental diabetes
Autor/es:
PAGOTTO, MELINA; ROLDÁN, LORENA; PAGOTTO, ROMINA; ROJIC, GASTÓN; MONZÓN, CASANDRA; MOLINAS, SARA; TRUMPER, LAURA; ELÍAS, M. MÓNICA; PIGNATARO, OMAR; MONASTEROLO, LILIANA
Lugar:
Milan
Reunión:
Congreso; World Congress of Nephrology 2009; 2009
Institución organizadora:
International Society of Nephrology
Resumen:
INTRODUCTION AND AIMS:Accumulative evidence suggests an important role for sex hormones in the pathophysiology of diabetic renal complications. Diabetes (DBT) was associated with altered plasma levels of progesterone (P4) and testosterone (T). A correlation between relative balance of sex hormones and the pathophysiology of renal disease was proposed.The aim of this study was to examine the effects of an early stage of DBT in rat kidney on: i) expression of the steroidogenic acute regulatory (StAR) protein, responsible for cholesterol delivery to the inner mitochondrial membrane; ii) steroidogenic capacity and iii) tissue contents of P4 and T.METHODS:Male adult Wistar rats received a single i.v. injection of streptozotocin (STZ) 50 mg/Kg or vehicle (C). After seven days (glucose plasma level: 3.8±0.8 g/l), kidneys were excised and cortex (CX) and medulla (MD) were obtained. i) Expression of mRNA StAR was evaluated by semi quantitative RT-PCR. ii) Isolated mitochondria were incubated in the presence of 22R-hydroxycholesterol (22R-HO) and P4 released into the medium was measured by radioimmunoassay (RIA). 22R-HO is a cholesterol substrate derivative that easily passes through cell membranes and it is directly available for the cytochrome P450-side chain cleavage enzyme (P450scc) leading to P5 production. P5 is a substrate for 3â-hydroxysteroid dehydrogenase (3â-HSD), which converts it to P4. iii) T and P4 tissue levels were quantitated by RIA in CX and MD from control and STZ-treated rats. Results are mean±SEM; n= 4-5 per group; *p<0.05.RESULTS:i) Expression of mRNA StAR decreased 1.8-fold and 3.4-fold in CX and MD, respectively, in STZ-treated rats, indicating that DBT induces a decrease in cholesterol import into the mitochondria and its availability to the P450scc.ii) P4 released into the medium, in the presence of 22R-HO, did not differ in CX, but was diminished in MD from STZ-treated rats with respect to the control (C:15.9±0.8; STZ:7.2±1.6* pg P4/ug protein) suggesting an inhibition of P450scc and/or 3â-HSD in MD from diabetic rats.iii) STZ treatment evoked a diminution in MD P4 content (C:28.7±6.2; STZ:12.1±2.9* pg/mg tissue) without changes in CX. T content was found decreased in CX (C:2.88±1.86; STZ:0.58±0.16* pg/mg tissue) and MD (C:4.28±1.70; STZ:0.59±0.35*). These data are consistent with the P4 synthesis described above. The decrease in T content in CX and MD could reflect some inhibition on other downstream enzymes in the steroidogenic pathway and it is in correlation with plasma T concentration (C:1.15±0.35; STZ:0.2±0.04* ng/ml).CONCLUSIONS:In conclusion, since nephrosteroids may act locally, in a paracrine or autocrine fashion, these alterations in the local steroidogenic machinery and sex hormone levels could contribute to the pathophysiology of renal disease in diabetes.