Liao D Z, Porsch-Hällström I, Gustafsson J A, Blanck A
Department of Medical Nutrition, Karolinska Institute, Huddinge, Sweden.
Hepatology. 1996 Apr;23(4):835-9. doi: 10.1002/hep.510230426.
The effects of gonadal hormones on several parameters associated with sex-differentiated promotion in the resistant hepatocyte (RH) model were studied. Male and female rats were initiated with diethylnitrosamine and promoted with 2-acetylaminofluorene (2-AAF) and partial hepatectomy [correction of hepatecomy] (PH). Before promotion, some female rats were ovariectomized, with or without receiving subcutaneous testosterone implants. Rats were killed either at the time of cessation of 2-AAF treatment or 2 weeks later. Ovariectomy decreased the messenger RNA (mRNA) expression of the female-specific cytochrome P450 2C12 (CYP2C12) at the time of PH, but did not increase the male-specific CYP2C11. Testosterone treatment further decreased CYP2C12 and induced CYP2C11 to the level in male liver. Hepatic foci positive for the placental form of glutathione-S-transferase (GST-P) were larger in male than in female rats. Ovariectomy did not affect the size of foci, whereas testosterone treatment increased the size to the male level. At the time of cessation of 2-AAF treatment, the labeling index, determined as cells staining for proliferating cell nuclear antigen, was higher in foci of males and testosterone-treated females than in foci from females with or without ovariectomy, whereas the labeling index in the surrounding hepatocytes was lower in males and testosterone-treated females. Two weeks later, the sex differences in labeling index were still present in foci, but no differences were observed in the surrounding hepatocytes. An elevated c-myc expression was observed in nodules isolated 3 weeks after PH from males and testosterone-treated females, but not in nodules from intact females. In conclusion, ovarian hormones did not affect promotion in the RH-model, whereas testosterone administration to ovariectomized females masculinized growth hormone-regulated hepatic parameters and response to promotion.
研究了性腺激素对耐药肝细胞（RH）模型中与性别分化促进相关的几个参数的影响。雄性和雌性大鼠先用二乙基亚硝胺启动，然后用2-乙酰氨基芴（2-AAF）和部分肝切除术（PH）进行促进。在促进之前，一些雌性大鼠进行了卵巢切除术，有无接受皮下睾酮植入物。大鼠在停止2-AAF治疗时或2周后处死。卵巢切除术在PH时降低了雌性特异性细胞色素P450 2C12（CYP2C12）的信使核糖核酸（mRNA）表达，但未增加雄性特异性CYP2C11。睾酮治疗进一步降低了CYP2C12，并将CYP2C11诱导至雄性肝脏中的水平。谷胱甘肽-S-转移酶（GST-P）胎盘形式阳性的肝灶在雄性大鼠中比雌性大鼠更大。卵巢切除术不影响病灶大小，而睾酮治疗将病灶大小增加到雄性水平。在停止2-AAF治疗时，以增殖细胞核抗原染色的细胞确定的标记指数在雄性和睾酮治疗的雌性病灶中高于有或无卵巢切除术的雌性病灶，而雄性和睾酮治疗的雌性周围肝细胞中的标记指数较低。两周后，病灶中标记指数的性别差异仍然存在，但在周围肝细胞中未观察到差异。在PH后3周从雄性和睾酮治疗的雌性中分离出的结节中观察到c-myc表达升高，但在完整雌性的结节中未观察到。总之，卵巢激素不影响RH模型中的促进作用，而对去卵巢雌性给予睾酮可使生长激素调节的肝脏参数和对促进的反应男性化。
