PCB 169 A Putative Antiandrogen

The PCB congener 169 is an Ah receptor agonist with a toxic equivalency factor of about 0.001, as compared to the potency of TCDD. PCB 169 treatment during pregnancy (administered as a single dose of 1.8 mg/kg to the dam on GD 8) alters reproductive development of LE hooded male and female rats in a manner almost identical to TCDD [115]. However, the sensitive androgen-dependent measures (AGD, areolas, and nipples) were not altered in treated males. Similar to TCDD treatment, PCB 169 treatment accelerated the age at eye opening and induced vaginal threads and mild hypospadias (urethral opening separate from the vaginal canal with cleft phallus) in female offspring, without reducing AGD or inducing areolas or nipples in males. In this regard, these organs were more affected in PCB 169-treated males at 65 days of age than in middle-aged males. PCB 169 treatment in utero increased the incidence of prostatitis in the dorsolateral lobe of the prostate of old male rats from 2/15 in controls to 7/10 in the treated males (p <0.01) [115].

It is evident that the overall profile of effects seen in TCDD- and PCB 169-treated male and female offspring bears only limited resemblance to that seen in animals exposed to known antiandrogens. The fact that PCB 169 treatment fails to reduce AGD and induce areolas, retained nipples, and male hypospadias, hallmarks of antiandrogenic action, at a dosage level that produces significant reproductive toxicity suggests that the Ah receptor agonists may be affecting these tissues via alternative pathways, ones that do not involve the androgens or their receptor. Many other growth factors (i.e., epidermal growth factor) and hormones (i.e., prolactin, thyroid, and growth hormones) also are required for maximal development of these tissues. In addition, PCB 169 and TCDD induce many effects that are clearly unrelated to androgen action (eye opening, and female effects like cleft phallus and vaginal threads).

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