Inhibition of rat testicular androgenesis by a polychlorinated biphenyl mixture aroclor 1248.
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 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/lyase, and 17beta-hydroxysteroid dehydrogenase activities.
Andric
S A
SA
Institute of Biology, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Serbia.
Kostic
T S
TS
Stojilkovic
S S
SS
Kovacevic
R Z
RZ
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000728:Androgens / Q000096:biosynthesis*; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013737:Testis / Q000187:drug effects* / Q000378:metabolism*; D013739:Testosterone / Q000097:blood / Q000378:metabolism
D000728:Androgens; D001140:Aroclors; D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; C028617:aroclor 1248; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D011284:Pregnenolone; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase