Inhibition of rat testicular androgenesis by a polychlorinated biphenyl mixture Aroclor 1248

Polychlorinated biphenyls (PCBs) are complex mixtures of congeners that exh ibit 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 pen tachloro congeners. Single intraperitoneal (i.p.) or bilateral intratesticu lar (i.t.) injections of A1248 decreased serum androgen levels in both grou ps 24 h after injection. Chorionic gonadotropin-stimulated androgen product ion by acute testicular cultures from both groups was also reduced, and pro gesterone 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 testos terone 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 wa s sufficient to attenuate the conversion of pregnenolone to progesterone an d progesterone to testosterone. At micromolar concentrations, A1248 added i n vitro also inhibited the conversion of Delta(4)-androstendione to testost erone without affecting the viability of interstitial cells. These results indicate that A1248 down-regulates the testicular androgenesis by an acute inhibition of 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase/lya se, and 17 beta-hydroxysteroid dehydrogenase activities.