Growth hormone modifies the growth rate of enzyme-altered hepatic foci in male rats treated according to the resistant hepatocyte model

Abstract

Male and female Wistar rats were given an initiating i.p. injection of diethylnitrosamine (DEN; 200 mg/kg body wt). Two weeks later the rats were given a diet containing 0.02% (w/w) 2-acetylaminofluorene (2-AAF) for 2 weeks. In the middle of the 2-AAF treatment a 70% partial hepatectomy (PH) was performed. In order to identify the pituitary hormone responsible for the previously observed sex difference (male > female) in and influence of ectopic pituitary grafts on focal growth during 2-AAF/PH selection of enzyme-altered foci, male rats were treated with a continuous infusion of bovine growth hormone (bGH: 6 .mu.g/h) or ovine prolactin (oPrl; 6 .mu.g/h) by way of osmotic minipumps. Hormonal treatment was started 1 week after initiation and was finished 1 week after the 2-AAF selection period. All rats were killed 6 weeks after initiation and liver sections were stained for .gamma.-glutamyltransferase. The number of foci/cm2 as well as the area per focus and area ratio (mm2 foci/cm2 liver section) were calculated. Whereas no significant differences in the number of foci/cm2 were observed between the different groups of rats, bGH treatment of male rats decreased both the area/focus and the area ratio down to the female level. No significant effects were seen following oPrl administration when compared with control males. In vitro studies of subcellular preparations from the liver lobes obtained at PH showed that the sexually differentiated N-hydroxy-2-AAF sulfotransferase activity (male > female) in male rats was ''feminized'', i.e. decreased, by bGH administration, but not by infusion of oPrl. The present investigation strengthens the view of growth hormone as an important determinant of sex differences in chemical carcinogenesis in rat liver, possibly via an influence on carcinogen metabolism.