Effects of gonadal steroid hormones on the hypothalamo-pituitary-liver axis in the control of sex differences in hepatic steroid metabolism in the rat.
Effects of gonadal steroid hormones on the hypothalamo-pituitary-liver axis in the control of sex differences in hepatic steroid metabolism in the rat.
复制标题
性腺类固醇激素对下丘脑-垂体-肝脏轴的影响控制大鼠肝脏类固醇代谢的性别差异。
作者：
A. Mode;G. Norstedt
通过测量（i）将雌二醇植入雄性垂体或下丘脑前部和（ii）在分化的雄性和雌性大鼠中皮下注射合成雄激素的影响，研究性腺激素在调节肝脏类固醇代谢中的作用位点。体外测量的肝脏反应是雄烯二酮的5α-还原、6β-和16α-羟基化。垂体内或下丘脑内植入雌二醇后，相对于植入胆固醇的动物的酶活性，雄性的5α-还原酶活性增加，6β-和16α-羟化酶活性降低，表明雌激素的女性化作用。这种效果不能通过皮下注射相同的雌激素制剂来实现。传入神经阻滞对女性肝脏类固醇代谢没有影响，但会导致男性女性化。此外，用合成雄激素对完整雌性进行皮下治疗会导致肝脏类固醇代谢男性化，但对分化动物没有影响。合成雄激素治疗对分化雄性动物的肝脏类固醇代谢没有影响。皮下注射强效合成孕激素对完整雌性的肝脏类固醇代谢几乎没有影响。结论是，雌激素通过下丘脑-垂体水平的作用使肝类固醇代谢女性化，并且合成雄激素对肝类固醇代谢的男性化作用需要完整的下丘脑-垂体轴。雄激素的作用部位可能位于下丘脑前部或大脑的邻近区域。
The site of action of gonadal hormones in the regulation of hepatic steroid metabolism was investigated by measuring the effects of (i) implantation of estradiol into the pituitary gland or anterior hypothalamus of males and (ii) subcutaneous injection of a synthetic androgen in differentiated male and female rats. The hepatic responses measured in vitro were 5 alpha-reduction, and 6 beta- and 16 alpha-hydroxylation of androstenedione. After intrapituitary or intrahypothalamic implantation of oestradiol, 5 alpha-reductase activity increased and 6 beta- and 16 alpha-hydroxylase activity decreased in males relative to the enzyme activities of cholesterol-implanted animals, indicating a feminizing effect of the oestrogen. This effect could not be accomplished by subcutaneous injection of the same oestrogen preparation. Deafferentation had no effect on hepatic steroid metabolism in females, but caused a feminization in males. In addition, subcutaneous treatment of intact females with the synthetic androgen caused masculinization of hepatic steroid metabolism, but was without effect in differentiated animals. Treatment with synthetic androgens had no effect on the hepatic steroid metabolism in differentiated male animals. Subcutaneous injection of a potent synthetic progestagen had little effect on hepatic steroid metabolism in intact females. It is concluded that oestrogen feminizes hepatic steroid metabolism by an action at the hypothalamic-pituitary level and that an intact hypothalamic-pituitary axis is required for the masculinizing action of the synthetic androgen on hepatic steroid metabolism. It is possible that the site of action of androgens is in the anterior hypothalamus or in adjacent areas of the brain.