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


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Castilla-Cortazar
Inma
I
Department of Human Physiology, School of Medicine, University of Navarra, Pamplona, Spain. iccortazar@uma.es
Diez
Nieves
N
Garcia-Fernandez
Maria
M
Puche
Juan-Enrique
JE
Diez-Caballero
Fernando
F
Quiroga
Jorge
J
Diaz-Sanchez
Matias
M
Castilla
Alberto
A
Casares
Amelia-Diaz
AD
Varela-Nieto
Isabel
I
Prieto
Jesus
J
Gonzalez-Baron
Salvador
S
D000818:Animals; D001284:Atrophy; D002251:Carbon Tetrachloride; D004967:Estrogens / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D007006:Hypogonadism / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000150:complications*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000378:metabolism / Q000473:pathology*; D013739:Testosterone / Q000097:blood; D014168:Transferrin / Q000378:metabolism
D004967:Estrogens; D014168:Transferrin; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002251:Carbon Tetrachloride