Blanck A, Eriksson L C, Gustafsson J A, Porsch Hällström I
Department of Medical Nutrition, Huddinge University Hospital, Karolinska Institute, Sweden.
Carcinogenesis. 1991 Jul;12(7):1259-64. doi: 10.1093/carcin/12.7.1259.
The previously observed sex difference in the growth rate of enzyme-altered foci (male greater than female) in rats treated according to the resistant hepatocyte model (RH model) occurs during selection/promotion of diethylnitrosamine-initiated cells with dietary 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH). The secretory pattern of growth hormone (GH) is sex dependent in the adult rat and is a major determinant for sex-differentiated liver functions. In the present study the capacity for liver regeneration following PH in the RH model was studied in rats of both sexes, in castrated males and in males receiving GH infusion, both treatments leading to a feminine pattern of GH secretion. Mitoinhibition during treatment with 2-AAF was shown to be more pronounced in liver from male than from female rats, both in initiated and non-initiated animals. Castration of male rats and continuous infusion of GH to males during the selection period, previously shown to decrease the focal growth rate towards that in female rats, 'feminized' also the degree of mitoinhibition. Autoradiography of sections from animals receiving continuous infusion of [3H]thymidine for 1 week, starting at the time of PH, demonstrated a lower labeling index in surrounding liver from male rats treated in the RH model than in surrounding liver from female rats. Males treated with continuous infusion of human GH during 2-AAF/PH treatment had an intermediary labeling index in the surrounding tissue. No differences in labeling index in enzyme-altered foci was observed between males, females or males plus hGH. These findings support the concept that sex-differentiated promotion in the RH model is exerted by selective mitoinhibition and that this feature is regulated by GH.
在根据抗性肝细胞模型（RH模型）处理的大鼠中，先前观察到的酶改变灶生长速率的性别差异（雄性大于雌性）发生在使用膳食2-乙酰氨基芴（2-AAF）和部分肝切除术（PH）对二乙基亚硝胺启动的细胞进行选择/促进过程中。成年大鼠生长激素（GH）的分泌模式具有性别依赖性，并且是性别分化肝功能的主要决定因素。在本研究中，对RH模型中PH后两性大鼠、去势雄性大鼠以及接受GH输注的雄性大鼠的肝再生能力进行了研究，这两种处理均导致GH分泌呈现雌性模式。结果显示，在使用2-AAF处理期间，无论是启动的还是未启动的动物，雄性大鼠肝脏中的线粒体抑制都比雌性大鼠更为明显。先前的研究表明，在选择期对雄性大鼠进行去势并持续输注GH，可使灶性生长速率降低至雌性大鼠的水平，同时也使线粒体抑制程度“雌性化”。从PH时开始连续1周接受[3H]胸苷输注的动物切片放射自显影显示，RH模型处理的雄性大鼠周围肝脏的标记指数低于雌性大鼠周围肝脏。在2-AAF/PH处理期间持续输注人GH的雄性大鼠，其周围组织的标记指数处于中间水平。在雄性、雌性或雄性加hGH组的酶改变灶中，未观察到标记指数的差异。这些发现支持了以下概念：RH模型中的性别分化促进作用是通过选择性线粒体抑制发挥的，并且这一特征受GH调节。
