Testicular function in uremic rats: in vivo 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 greater than 30 mmol/l, creatinine clearance less than 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.
Blacker
C
C
Fondation de Recherche en Hormonologie, Paris, France.
Provost
M
M
Kerdelhue
B
B
Scholler
R
R
D019326:17-alpha-Hydroxyprogesterone; D000735:Androstenedione / Q000097:blood; D000818:Animals; D001835:Body Weight; D003404:Creatinine / Q000652:urine; D006908:Hydroxyprogesterones / Q000097:blood; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D011374:Progesterone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000503:physiopathology*; D013739:Testosterone / Q000096:biosynthesis* / Q000097:blood; D014511:Uremia / Q000097:blood / Q000503:physiopathology*
D006908:Hydroxyprogesterones; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D003404:Creatinine