Inhibition of Rat Testicular Androgenesis by a Polychlorinated Biphenyl Mixture Aroclor 1248

• Published in: Biology of reproduction Vol. 62; no. 6; pp. 1882 - 1888
• Main Authors: ANDRIC, S. A, KOSTIC, T. S, STOJILKOVIC, S. S, KOVACEVIC, R. Z
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01.06.2000
• Subjects: 17-Hydroxysteroid Dehydrogenases - antagonists & inhibitors; 3-Hydroxysteroid Dehydrogenases - antagonists & inhibitors; Androgens - biosynthesis; Androstenedione - metabolism; Animals; Aroclors - pharmacology; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Chorionic Gonadotropin - pharmacology; Dihydrotestosterone - blood; Enzyme Inhibitors - pharmacology; Male; Medical sciences; Pregnenolone - metabolism; Progesterone - metabolism; Rats; Rats, Wistar; Steroid 17-alpha-Hydroxylase - antagonists & inhibitors; Testis - drug effects; Testis - metabolism; Testosterone - blood; Testosterone - metabolism; Toxicology; Various organic compounds; Androgen; Rat; Toxicity; Rodentia; Testicle; Polychlorobiphenyl; In vitro; In vivo; Pollutant; Vertebrata; Mammalia; Animal; Steroidogenesis; Sex steroid hormone; Mechanism of action
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod62.6.1882

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 Δ 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 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/lyase, and 17β-hydroxysteroid dehydrogenase activities.