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Silvana A. Andric,¹ Tatjana S. Kostic,¹ Snezana M. Dragisic,¹ Nebojsa L. Andric,¹ Stanko S. Stojilkovic,² and Radmila Z. Kovacevic¹

¹Institute of Biology, Faculty of Sciences, Serbia, Yugoslavia
²Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, USA

Abstract

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 µg/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-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 µg/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. Key words: 3ß-hydroxysteroid dehydrogenase, androgen, P450c17, polychlorinated biphenyls, progesterone. Environ Health Perspect 108:955-959 (2000) . [Online 5 September 2000]

http://ehpnet1.niehs.nih.gov/docs/2000/108p955-959andric/ abstract.html

Address correspondence to R. Kovacevic, Institute of Biology, Faculty of Sciences, 2 Dositeja Obradovica Square, 21000 Novi Sad, Serbia, Yugoslavia. Telephone: 381-21-58-988. Fax: 381-21-450-620. E-mail: radmilak@unsim.ns.ac.yu

We thank J. Cochran, S. Kapor, and V. Djordjevic-Milic for characterization of Askarel used in these experiments, and G.D. Niswender for the supply of antiserum. We also thank L. Hansen for continuous support and help in work on PCB actions in steroidogenic tissue.

Received 28 April 2000 ; accepted 31 May 2000.