Insulin-like growth factor-I reverts testicular atrophy in rats with advanced cirrhosis.
The pathogenesis of hypogonadism in cirrhosis is not completely understood. The levels of insulin-like growth factor-I (IGF-I), an anabolic factor with trophic actions on testes, are reduced in cirrhosis. This study was undertaken to evaluate whether rats with advanced cirrhosis develop hypogonadism and whether the administration of IGF-I exerts beneficial effects on testicular structure and function. Wistar rats with ascitic cirrhosis induced with CCl(4) were allocated into 2 groups (n = 10, each) to receive recombinant IGF-I (20 microg x kg(-1) x d(-1), subcutaneously) or vehicle for 3 weeks. Healthy rats receiving vehicle were used as the control group (n = 10). At baseline, both cirrhotic groups showed similar deterioration of liver function tests. Compared with controls, nontreated cirrhotic rats showed decreased serum levels of IGF-I (P <.05), reduced testicular size and weight (P <.001), and intense histopathological testicular abnormalities, including reduced tubular diameters (P <.001), loss of the germinal line (P <. 001), and diminutions in cellular proliferation, spermatogenesis (P <.001), and testicular transferrin expression (P <.001). In addition, low serum testosterone (P <.01) and high serum LH (P <.01) were present in untreated cirrhotic animals. Cirrhotic rats that received IGF-I showed full recovery of testicular size and weight and of all histopathological abnormalities (P <.001 to <.01 vs. nontreated cirrhotic rats; P = ns vs. controls). Serum levels of sex hormones tended to normalize. In conclusion, IGF-I deficiency may play a pathogenetic role in hypogonadism of cirrhosis. Low doses of IGF-I for a short period of time revert testicular atrophy and appear to improve hypogonadism in advanced experimental cirrhosis.
Castilla-Cortazar
I
I
Department of Physiology, Liver Unit, University of Navarra, Pamplona, Spain. icastill@uma.es
Garcia
M
M
Quiroga
J
J
Diez
N
N
Diez-Caballero
F
F
Calvo
A
A
Diaz
M
M
Prieto
J
J
D000818:Animals; D001835:Body Weight; D004798:Enzymes / Q000097:blood; D006728:Hormones / Q000097:blood; D007006:Hypogonadism / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000494:pharmacology*; D008106:Liver Cirrhosis, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014168:Transferrin / Q000032:analysis
D004798:Enzymes; D006728:Hormones; D018809:Proliferating Cell Nuclear Antigen; D014168:Transferrin; D007334:Insulin-Like Growth Factor I