TESTICULAR FUNCTION IN UREMIC RATS - INVIVO ASSESSMENT OF TESTOSTERONE BIOGENESIS

The mechanism of testosterone (T) production defect in uremic rats has not yet been clearly defined and hypothalamo-hypophyseal impairment as well as primary testicular dysfunction have been suggested. In 42 rats followed monthly after subtotal nephrectomy up to 7.1 +/- 0.3 months, we observed a progressive significant decline of T and androstenedione (A) compared to control rats. Two months before the terminal phase of chronic renal failure (CRF), T/A ratio abruptly declined. T and its precursors on the 4-ene pathway, A, progesterone (P) and 17-hydroxyprogesterone were evaluated in pampiniform plexus testicular vein (PPTV) and in peripheral blood (PV) in end stage uremic rats (blood urea > 30 mmol/l, creatinine clearance < 0.5 ml/min). Under basal conditions, all steroids but peripheral P were significantly lower in uremic rats than in controls as well as T/P and A/P ratios. After human chorionic gonadotropin (hCG) stimulation, T concentration in PV and PPTV remained highly significantly lower than in controls whereas T precursor concentrations were partially corrected by hCG administration. T/P ratio remained lower than in controls whereas A/P ratio was not significantly lower than in controls. Those data show a decline in all the steps of T biogenesis in uremic rats in basal conditions. The defect in 17-beta-hydroxysteroid dehydrogenase evidenced by T/A decrease at the end stage of CRF seems of primary testicular origin as it is not corrected by hCG administration as shown by T/P and A/P ratios in PPTV and in PV.