Hematotesticular barrier is altered from early stages of liver cirrhosis: effect of insulin-like growth factor 1

• Published in: World journal of gastroenterology : WJG Vol. 10; no. 17; pp. 2529 - 2534
• Main Authors: Castilla-Cortazar, Inma, Diez, Nieves, Garcia-Fernandez, Maria, Puche, Juan-Enrique, Diez-Caballero, Fernando, Quiroga, Jorge, Diaz-Sanchez, Matias, Castilla, Alberto, Casares, Amelia-Diaz, Varela-Nieto, Isabel, Prieto, Jesus, Gonzalez-Baron, Salvador
• Format: Journal Article
• Language: English
• Published: United States Department of Human Physiology, University of Navarra, Pamplona, Navarra, Spain 01.09.2004; Department of Human Physiology, School of Medicine, University of Málaga,Malaga, Spain%Department of Human Physiology, University of Navarra, Pamplona, Navarra, Spain%Department of Human Physiology, School of Medicine, University of Málaga,Malaga, Spain%Department of Internal Medicine,Liver Unit, University of Navarra, Pamplona, Navarra, Spain%Department of Internal Medicine, Hospital Sierrallana, Tollelavega and School of Medicine, University of the Basque Country-Vitoria-Gasteiz, Spain%Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Cientificas Universidad Autónoma de Madrid (CSIC-UAM), Madrid, Spain; Baishideng Publishing Group Inc
• Subjects: Animals; Atrophy; Carbon Tetrachloride; Clinical Research; Estrogens - blood; Follicle Stimulating Hormone - blood; Hypogonadism - drug therapy; Hypogonadism - etiology; Hypogonadism - pathology; Insulin-Like Growth Factor I - pharmacology; Liver Cirrhosis - complications; Luteinizing Hormone - blood; Male; Pituitary Gland - metabolism; Rats; Rats, Wistar; Sertoli Cells - metabolism; Sertoli Cells - pathology; Testis - metabolism; Testis - pathology; Testosterone - blood; Transferrin - metabolism
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v10.i17.2529

The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis. The aim of this study was to establish the historical progression of the described alterations in the testes, explore testicular morphology, histopathology, cellular proliferation, integrity of testicular barrier and hypophyso-gonadal axis in rats with no ascitic cirrhosis. Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride (CCl4) for 11 wk, were allocated into two groups (n = 12, each) to receive recombinant IGF-1 (2 microg/100 g.d, sc) for two weeks or vehicle. Healthy rats receiving vehicle were used as control group (n = 12). Compared to controls, rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities. However, these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression. In addition, pituitary-gonadal axis was altered, with significant higher levels of FSH (P<0.001 vs controls) and increased levels of LH in untreated cirrhotic animals. Interestingly, IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH (P = ns vs controls, and P<0.01 vs untreated cirrhotic group). The testicular barrier is altered from an early stage of cirrhosis, shown by a reduction of transferrin expression in Sertoli cells, a diminished cellular proliferation and an altered gonadal axis. The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.