Chung K W
Department of Anatomical Sciences, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma.
Life Sci. 1989;44(4):273-80. doi: 10.1016/0024-3205(89)90185-9.
The purpose of this study was to investigate ethanol-induced changes in androgen receptor sites in the anterior pituitary, hypothalamus, and brain cortex. Young adult male King-Holtzman rats were fed for 5 months a nutritionally complete liquid diet, with ethanol or isocaloric sucrose constituting 36% of the total calories. Androgen receptor sites were measured by sucrose density gradient and charcoal assay using tritiated dihydrotestosterone (DHT). Scatchard plot analysis of the data revealed that apparent dissociation constants of DHT-receptor complex for the anterior pituitary, hypothalamus, and brain cortex from alcohol-fed animals were estimated to be 0.7 +/- 0.13, 0.6 +/- 0.16 and 0.9 +/- 0.15 nM, respectively. These values are identical to those of their isocaloric controls. The concentrations of cytosol androgen receptors of the pituitary, hypothalamus, and brain cortex from alcohol-fed rats were 8.0 +/- 1.2, 6.2 +/- 1.0 and 4.9 +/- 0.7 fmol/mg protein, respectively. This represents about a 34, 24, and 22% reduction when compared to the values of the isocaloric control animals. In contrast to control rats, neither castration nor androgen or LHRH replacement to castrated alcohol-fed rats altered an alcohol-induced reduction of androgen receptor contents. Serum LH and testosterone levels were significantly decreased in alcohol-fed rats but these hormone levels were increased by administration of LHRH or norepinephrine. Such reduction of androgen receptors, serum LH and testosterone, but enhancement of these hormone levels by treatment with neurohormone and neurotransmitter in these animals suggests that ethanol exerts an adverse effect on the hypothalamic-pituitary unit and the neurotransmitter-hypothalamic hormone relationship, resulting in impairment of the androgen-induced sexual events and a suppression of the pituitary gonadotropin secretion.
本研究的目的是调查乙醇诱导的垂体前叶、下丘脑和大脑皮层中雄激素受体位点的变化。将年轻成年雄性King-Holtzman大鼠用营养完全的液体饲料喂养5个月,其中乙醇或等热量蔗糖占总热量的36%。使用氚标记的二氢睾酮(DHT)通过蔗糖密度梯度和活性炭分析法测量雄激素受体位点。对数据的Scatchard图分析显示,来自喂食酒精动物的垂体前叶、下丘脑和大脑皮层的DHT-受体复合物的表观解离常数估计分别为0.7±0.13、0.6±0.16和0.9±0.15 nM。这些值与其等热量对照的数值相同。来自喂食酒精大鼠的垂体、下丘脑和大脑皮层的胞质雄激素受体浓度分别为8.0±1.2、6.2±1.0和4.9±0.7 fmol/mg蛋白质。与等热量对照动物的值相比,这分别代表约34%、24%和22%的降低。与对照大鼠相反,去势以及对去势的喂食酒精大鼠给予雄激素或促性腺激素释放激素(LHRH)均未改变酒精诱导的雄激素受体含量降低。喂食酒精的大鼠血清促黄体生成素(LH)和睾酮水平显著降低,但通过给予LHRH或去甲肾上腺素可使这些激素水平升高。这些动物中雄激素受体、血清LH和睾酮的这种降低,但通过神经激素和神经递质治疗使这些激素水平升高,表明乙醇对下丘脑-垂体单位以及神经递质-下丘脑激素关系产生不利影响,导致雄激素诱导的性活动受损以及垂体促性腺激素分泌受到抑制。