Persico M, Bellentani S, Marchegiano P, Orzes N, Lunazzi G C, Sottocasa G L, Tiribelli C
Dipartimento Biochimica, University of Trieste, Italy.
J Hepatol. 1988 Jun;6(3):343-9. doi: 10.1016/s0168-8278(88)80052-7.
To investigate the role of sex steroids in the sex-related difference in the hepatic uptake of organic anions, sulphobromophthalein (bromsulphalein, BSP) transport was measured in hepatocytes isolated from rats either deprived of hormonal influence by castration at prepubertal age or after hormonal substitution. In control animals, the kinetics of BSP uptake showed the presence of two components: one saturable (0-3 microM), with high affinity and low capacity, and the other linear (9-30 microM), probably related to the non-specific component of BSP uptake. Sex difference was detected only in the saturable portion of the uptake process as the apparent Km was significantly lower in females than in males (3.8 +/- 0.7 vs. 6.1 +/- 1.8 microM, mean +/- S.D. of six animals, P less than 0.01). In contrast, no difference was observed in Vmax (2.3 +/- 0.3 vs. 2.2 +/- 0.7 nmol BSP.(mg protein)-1.min-1). Castration was associated with the disappearance of the saturable uptake site and abolished the sex difference. Progesterone treatment of castrated males failed to restore the saturable kinetics of BSP uptake. In contrast, administration of oestradiol to castrated males or testosterone to castrated females did restore the saturable kinetics of the high-affinity BSP uptake. Km and Vmax were comparable to those of adult females and males, respectively, with the exception of testosterone which induced a Vmax value higher than that observed in the other groups of animals. These data suggest that the influence of oestrogen and testosterone is necessary for the expression of the high-affinity, low-capacity carrier-mediated process of hepatic BSP uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
为研究性类固醇在肝脏摄取有机阴离子的性别差异中所起的作用，对从青春期前阉割以消除激素影响或进行激素替代后的大鼠分离出的肝细胞中的磺溴酞钠（酚四溴酞磺酸钠，BSP）转运进行了测定。在对照动物中，BSP摄取动力学显示存在两个成分：一个是可饱和的（0 - 3微摩尔），具有高亲和力和低容量，另一个是线性的（9 - 30微摩尔），可能与BSP摄取的非特异性成分有关。仅在摄取过程的可饱和部分检测到性别差异，因为雌性的表观Km显著低于雄性（3.8±0.7对6.1±1.8微摩尔，六只动物的平均值±标准差，P<0.01）。相比之下，Vmax未观察到差异（2.3±0.3对2.2±0.7纳摩尔BSP·(毫克蛋白)-1·分钟-1）。阉割导致可饱和摄取位点消失，并消除了性别差异。对阉割的雄性给予孕酮未能恢复BSP摄取的可饱和动力学。相反，对阉割的雄性给予雌二醇或对阉割的雌性给予睾酮确实恢复了高亲和力BSP摄取的可饱和动力学。Km和Vmax分别与成年雌性和雄性相当，睾酮诱导的Vmax值除外，其高于其他动物组观察到的值。这些数据表明，雌激素和睾酮的影响对于肝脏BSP摄取的高亲和力、低容量载体介导过程的表达是必要的。（摘要截断于250字）
