The Role of Testicular Aromatase in the Atrazine Mediated Changes of Estrone and Estradiol in the Male Wistar Rat.

Abstract

The impetus for this study was provided by previous reports that the chloro-s-triazine herbicide, atrazine, alters the serum concentrations of estrone and estradiol in rats after in vivo exposure and increases aromatase activity and the levels of the aromatase gene transcript CYP19 mRNA in the H295R cell line following in vitro exposure. Serum steroids (progesterone, corticosterone, androstenedione, testosterone, estrone and estradiol) were measured in 60-day-old, male Wistar rats following a single (3, 6, and 24 hrs after dosing) or multiple (2, 3, 4, or 21 days) doses of atrazine [0 (vehicle), 50 or 200 mg/kg, oral]. Hypothalamic and testicular CYP19 mRNA were evaluated by real time RT-PCR for each time point. In addition, aromatase activity was measured using the tritiated water assay in testicular microsomes following in vitro and in vivo exposure to atrazine. These studies show that atrazine not only altered serum estrogens, but also caused significant increases in serum androgens, progesterone, and corticosterone. Estrogen precursors, androstenedione and testosterone, were increased in both atrazine groups as early as 6 hrs after a single dose. Within 24 hrs, the changes in androgen concentrations dissipated. Serum corticosterone was significantly elevated in the highest treatment group at all but two of the six time points. Elevated estrone and estradiol were consistently observed as early as the 3rd day of exposure, but no changes in CYP19 mRNA were observed at any time point in either tissue. Nor did atrazine affect the levels of aromatase activity in testicular microsomes following in vitro or in vivo exposure. A subsequent study using castrated male rats demonstrated that the effect on serum estrogens is not due to testicular steroidogenesis. Rather, these data suggest that an atrazine mediated stress-induced adrenal response and/or a change in steroid synthesis or elimination may be responsible for the increase in serum steroids observed following exposure to atrazine.