Hälström I P, Liao D, Gustafsson J A, Blanck A
Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Sweden.
Carcinogenesis. 1994 May;15(5):921-5. doi: 10.1093/carcin/15.5.921.
The influence of implantation of ectopic pituitary grafts (PGs) under the kidney capsule in male rats on the sex differences in response to promotion with a choline-deficient (CD) diet was studied in the livers of diethylnitrosamine (DEN)-initiated Wistar rats. Growth of enzyme-altered foci, liver regeneration in response to partial hepatectomy (PH) and hepatic c-myc expression were studied. The area per enzyme-altered focus was significantly larger in initiated males fed a CD diet for 10 weeks when compared with the corresponding females. The sex difference was more pronounced 1 week after a PH performed following 10 weeks on the diet. In males carrying PGs the area per focus was reduced to the same size as in females. Liver weight gain after PH was reduced in males, but not in females, by the CD diet, and the level in PG-bearing males was intermediary, significantly different from that of males without grafts. A significantly lower labeling index in surrounding, but not in focal, hepatocytes was observed in initiated, CD-treated males than in the corresponding females 1 week after PH. In initiated as well as in uninitiated males on a CD diet the expression of the c-myc gene was 3- to 4-fold higher when compared with males fed a choline-supplemented diet at the time of PH. The mRNA level in females fed a CD diet was approximately 2.5-fold lower than in males, but still significantly above the level in females without the dietary treatment. A significant decrease in male c-myc expression was observed as a result of implantation of ectopic pituitaries. In conclusion, sex-differentiated promotion of DEN-initiated lesions with a CD diet is regulated by a pituitary influence on rat liver, in analogy with results previously obtained in the resistant hepatocyte model and with dietary deoxycholic acid promotion. This might suggest that pituitary factors are major determinants of sex-differentiated promotion in rat liver.
在二乙基亚硝胺（DEN）启动的Wistar大鼠肝脏中，研究了雄性大鼠肾被膜下植入异位垂体移植物（PGs）对胆碱缺乏（CD）饮食促进作用反应中性别差异的影响。研究了酶改变灶的生长、部分肝切除（PH）后的肝脏再生以及肝脏c-myc表达。与相应雌性相比，给予CD饮食10周的启动雄性大鼠，每个酶改变灶的面积显著更大。在饮食10周后进行PH，1周后性别差异更为明显。携带PGs的雄性大鼠每个灶的面积减小至与雌性相同大小。CD饮食使雄性大鼠PH后的肝脏重量增加减少，但雌性大鼠未受影响，携带移植物的雄性大鼠的肝脏重量增加处于中间水平，与未移植的雄性大鼠有显著差异。PH后1周，在启动的、接受CD处理的雄性大鼠中观察到，周围肝细胞（而非灶性肝细胞）的标记指数显著低于相应雌性。在启动的以及未启动的给予CD饮食的雄性大鼠中，与PH时给予胆碱补充饮食的雄性相比，c-myc基因的表达高出3至4倍。给予CD饮食的雌性大鼠的mRNA水平比雄性低约2.5倍，但仍显著高于未进行饮食处理的雌性大鼠。异位垂体植入导致雄性c-myc表达显著降低。总之，与先前在抗性肝细胞模型和饮食脱氧胆酸促进作用中获得的结果类似，CD饮食对DEN启动病变的性别分化促进作用受垂体对大鼠肝脏的影响调节。这可能表明垂体因子是大鼠肝脏性别分化促进作用的主要决定因素。
