Vanden Heuvel J P, Davis J W, Sommers R, Peterson R E
Environmental Toxicology Center, University of Wisconsin, Madison 53706.
J Biochem Toxicol. 1992 Spring;7(1):31-6. doi: 10.1002/jbt.2570070107.
There is a marked sex difference in the whole-body elimination of perfluorooctanoic acid (PFOA) in rats, with females excreting the perfluorinated acid much more rapidly (half life [t1/2] less than 1 day) than males (t1/2 = 15 days). Our objective was to determine if androgens or estrogens are involved in causing this sex difference in PFOA elimination. Castration of males greatly increased the elimination of [1-14C]PFOA (9.4 mumol/kg, i.p.) in urine, demonstrating that a factor produced by the testis was responsible for the slow elimination of PFOA in male rats. Castration plus 17 beta-estradiol had no further effect on PFOA elimination whereas castration plus testosterone replacement at the physiologic level reduced PFOA elimination to the same level as rats with intact testes. Thus, in male rats, testosterone exerts an inhibitory effect on renal excretion of PFOA. In female rats, neither ovariectomy nor ovariectomy plus testosterone affected the PFOA urinary elimination, demonstrating that the inhibitory effect of testosterone on PFOA renal excretion is a male-specific response. Probenecid decreased the high rate of PFOA renal excretion in castrated males but had no effect on male rats with intact testes. We conclude that testosterone is a key determinant of the sex difference in PFOA elimination in rats.
大鼠体内全氟辛酸（PFOA）的全身消除存在明显的性别差异，雌性排泄这种全氟化物的速度比雄性快得多（半衰期[t1/2]小于1天，而雄性的t1/2 = 15天）。我们的目的是确定雄激素或雌激素是否与PFOA消除的这种性别差异有关。对雄性大鼠进行去势手术极大地增加了尿液中[1-14C]PFOA（9.4 μmol/kg，腹腔注射）的消除，表明睾丸产生的一种因子是雄性大鼠中PFOA消除缓慢的原因。去势加17β-雌二醇对PFOA的消除没有进一步影响，而去势加生理水平的睾酮替代则将PFOA的消除降低到与睾丸完整的大鼠相同的水平。因此，在雄性大鼠中，睾酮对PFOA的肾脏排泄具有抑制作用。在雌性大鼠中，卵巢切除术以及卵巢切除术加睾酮均未影响PFOA的尿液消除，表明睾酮对PFOA肾脏排泄的抑制作用是雄性特有的反应。丙磺舒降低了去势雄性大鼠中PFOA的高肾脏排泄率，但对睾丸完整的雄性大鼠没有影响。我们得出结论，睾酮是大鼠PFOA消除性别差异的关键决定因素。
