Dithicarbamate Fungicide Thiram Disrupts the Hormonal Control of Ovulation in theFemale Rat

摘要

Thiram has been reported to inhibit dopamine-beta-hydroxylase and norepinephrine(NE) synthesis. NE is a neurotransmitter important to the control of pituitary function. In the study, the acute effects of thiram on the hormonal control of ovulation (luteinizing hormone (LH) surge) in the rat were investigated. Ovariectomized, estrogen-primed female rats received a single injection of thiram (0, 6, 12, 25, 50, and 100 mg/kg, i.p.) at 1100 h and serum LH was measured by serial bleeding. Thiram at 50 and 100 mg/kg completely blocked the LH surge in all rats, while 12 and 25 mg/kg blocked the surge in 40 and 75%, respectively. Six mg/kg had no effect. Ovulation was assessed in intact rats after dosing with 0, 12, 25, or 50 mg/kg thiram at 0900, 1100, 1300, or 1800 h on vaginal proestrus. 25 and 50 mg/kg at 1300 h blocked ovulation in all rats, but when injected at 1100 h, only 50 mg/kg was effective. Ovulation was unaltered by 50 mg/kg injections at 0900 or 1800 h. To determine the effects of thiram on the LH surge in intact rats, additional females were dosed at 1300 h on proestrus and blood collected over the same day. Thiram at 50 mg/kg blocked the LH surge in all rats, while 25 mg/kg blocked the surge in 60% of the females tested; 12 mg/kg had no effect. These data indicate that a sensitive period exists on the day of vaginal proestrus during which the hormonal control of ovulation can be disrupted by thiram.