Andric S A, Kostic T S, Dragisic S M, Andric N L, Stojilkovic S S, Kovacevic R Z
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Environ Health Perspect. 2000 Oct;108(10):955-9. doi: 10.1289/ehp.00108955.
Polychlorinated biphenyl (PCB)-based transformer fluids belong to a class of environmentally persistent mixtures with known toxic effects. Here, we studied the acute effects of Askarel (which contains Aroclor 1260) and two substitute transformer fluids (the silicone oil-based DC561 and the mineral oil-based ENOL C) on rat testicular steroidogenesis. Single intraperitoneal (ip; 10 mg/kg body weight) or bilateral intratesticular (itt; 25 microg/testis) injections of Askarel markedly decreased serum androgen levels 24 hr after administration. In acute testicular cultures from these animals, chorionic gonadotropin-stimulated progesterone and androgen productions were severely attenuated. When itt was injected or added in vitro, Askarel inhibited 3ss-hydroxysteroid dehydrogenase (3ssHSD), stimulated 17[alpha]-hydroxylase/lyase (P450c17), and did not affect 17ss-hydroxysteroid dehydrogenase in testicular postmitochondrial fractions. The ip-injected Askarel did not affect 3ssHSD, but inhibited P450c17, suggesting that a more intensive metabolism of peripherally injected Askarel reduces the circulating levels of active ingredients below the threshold needed for inhibition of 3ssHSD and generates a derivative that inhibits P450c17. In contrast to Askarel, itt-injection (25 microg/testis) of DC561 and ENOL C did not affect in vivo and in vitro steroidogenesis. These findings show the acute effects of Askarel, but not silicone and mineral oils, on testicular steroidogenesis.
基于多氯联苯(PCB)的变压器油属于一类具有已知毒性作用的环境持久性混合物。在此,我们研究了Askarel(含有Aroclor 1260)以及两种替代变压器油(硅油基DC561和矿物油基ENOL C)对大鼠睾丸类固醇生成的急性影响。单次腹腔注射(ip;10毫克/千克体重)或双侧睾丸内注射(itt;25微克/睾丸)Askarel后24小时,血清雄激素水平显著降低。在这些动物的急性睾丸培养物中,绒毛膜促性腺激素刺激的孕酮和雄激素生成严重减弱。当进行睾丸内注射或体外添加时,Askarel抑制3β-羟基类固醇脱氢酶(3βHSD),刺激17α-羟化酶/裂解酶(P450c17),并且不影响睾丸线粒体后组分中的17β-羟基类固醇脱氢酶。腹腔注射的Askarel不影响3βHSD,但抑制P450c17,这表明外周注射的Askarel的更强代谢将活性成分的循环水平降低到抑制3βHSD所需的阈值以下,并产生一种抑制P450c17的衍生物。与Askarel相反,睾丸内注射(25微克/睾丸)DC561和ENOL C在体内和体外均不影响类固醇生成。这些发现表明Askarel而非硅油和矿物油对睾丸类固醇生成具有急性影响。