The Derivative of Diesel Exhaust Particles, 4-Nitro-3-Phenylphenol, Exerts Both Androgenic and Anti-Androgenic Effect in Castrated Immature Male Rats

Abstract

This study investigated the effect of 4-nitro-3-phenylphenol (PNMPP) on testosterone-implanted castrated rats for 7 days. Exp I: The rats were injected with PNMPP at high doses (0.1, 1 and 10 mg/kg). Exp II: The rats were injected with low doses (0.001 and 0.01 mg/kg) or flutamide (4 mg/kg). The results show that at 10 mg/kg, PNMPP induced a significant increase in serum testosterone concentration, whereas treatment at 0.1, 1 and 10 mg/kg slightly increased adrenal gland weight (P > 0.5). Liver weight in the rats treated with 10 mg/kg was insignificantly decreased, which might reduce enzyme elimination. Moreover, serum corticosterone concentration in the rat treated with 10 mg/kg showed a decrease insignificantly (P >
0.5). Adrenal gland weight increased insignificantly (P > 0.5). PNMPP might mimic androgens effect on the hypothalamus-pituitary-adrenal feedback loop to glucocorticoid, resulting in decreased corticosterone concentration. PNMPP treatment at 10 mg/kg induced significant decreases in serum FSH and LH concentrations and had a trend toward a decrease when treated with 0.1 and 1.0 mg/kg. We presumed that PNMPP treatment at 10 mg/kg disturbed the hypothalamus-pituitary axis by decreasing gonadotropin concentrations. Furthermore, prolactin (PRL) concentration increased in the rats in a dose-dependent manner. This result supports the effect of PNMPP on hypothalamus-pituitary axis by directly increasing PRL
concentration. The weight of reproductive organs and kidneys in rats treated with high doses also showed androgenic effect by increasing significantly. The lower doses showed anti-androgenic effect by inducing a significant increase in serum FSH concentration in a dose-dependent manner and an insignificant increase in serum LH concentration of the rats, similar to flutamide effect. These substances furthermore reduced organ weight. We concluded that PNMPP possessed biphasic effects; it was androgenic at high doses and antiandrogenic at low doses.