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Biology of Reproduction 62, 1882-1888 (2000)
© 2000 Society for the Study of Reproduction, Inc.


Regular Article

Inhibition of Rat Testicular Androgenesis by a Polychlorinated Biphenyl Mixture Aroclor 12481

Silvana A. Andrica, Tatjana S. Kostica, Stanko S. Stojilkovicb, and Radmila Z. Kovacevic2,,b

a Institute of Biology, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Serbia b Endocrinology and Reproduction Research Branch, NICHD, Bethesda, Maryland 20892

ABSTRACT

Polychlorinated biphenyls (PCBs) are complex mixtures of congeners that exhibit carcinogenic and toxicant activities in a variety of mammalian tissues. Here, we studied the acute in vivo and in vitro effects of a commercially used PCB product, Aroclor 1248 (A1248), a mixture of tri-, tetra-, and pentachloro congeners. Single intraperitoneal (i.p.) or bilateral intratesticular (i.t.) injections of A1248 decreased serum androgen levels in both groups 24 h after injection. Chorionic gonadotropin–stimulated androgen production by acute testicular cultures from both groups was also reduced, and progesterone production was attenuated in cultures from i.t.-treated animals. The capacity of the postmitochondrial fractions from testes of i.t.-treated animals to convert pregnenolone to progesterone and progesterone to testosterone was reduced as well. In vitro studies revealed that a 10- to 15-min exposure of postmitochondrial testicular fractions and intact interstitial cells from normal animals to A1248 in a subnanomolar concentration range was sufficient to attenuate the conversion of pregnenolone to progesterone and progesterone to testosterone. At micromolar concentrations, A1248 added in vitro also inhibited the conversion of {Delta}4-androstendione to testosterone without affecting the viability of interstitial cells. These results indicate that A1248 down-regulates the testicular androgenesis by an acute inhibition of 3ß-hydroxysteroid dehydrogenase, 17{alpha}-hydroxylase/lyase, and 17ß-hydroxysteroid dehydrogenase activities.

FOOTNOTES

First decision: 18 November 1999.

1 A grant from the Serbia Research Association supported this research.

2 Correspondence: R.Z. Kovacevic, ERRB, NICHD, NIH, Bldg. 49, Room 6A-36, 49 Convent Drive, Bethesda, MD 20892-4510. FAX: 301 594 7031; radmilak{at}unsim.ns.ac.yu




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