BLOCKADE OF OVULATION IN THE RAT BY SYSTEMIC AND OVARIAN INTRABURSAL ADMINISTRATION OF THE FUNGICIDE SODIUM DIMETHYLDITHIOCARBAMATE

Dithiocarbamates, acting as inhibitors of catecholamine synthesis, hav e been reported to block ovulation in female rats following systemic a dministration by suppressing the neural noradrenergic signaling involv ed in triggering the ovulatory surge of luteinizing hormone. The ovari es also synthesize norepinephrine and receive noradrenergic input via sympathetic innervation, and it has been suggested that such input may play a role in follicular maturation and ovulation. The current exper iments investigated whether the dithiocarbamate fungicide dimethyldith iocarbamate (DMDTC) would block oocyte release in normally cycling rat s when administered systemically during the proestrous presurge period , and if so, would the compound also have a comparable direct ovarian effect on ovulation in response to a local intrabursal exposure of one ovary late on the day of vaginal proestrus, The results showed that a dose-related suppression of oocyte release was present in response to both intraperitoneal and intrabursal (IB) injections, But these effec ts appear to be mediated through different mechanisms, The unilateral IB injections mere effective only on the exposed side for each ovarian pair, while no alterations were seen in ovarian norepinephrine, IB ad ministration 24 h earlier blocked ovulation on both sides, while hCG i njections were able to restore ovulation on the noninjected side only, implying that diestrous DMDTC was inhibiting the LH surge. The data i ndicate that while an effect on hypothalamic catecholamine synthesis m ay underlie the ovulatory blockade following intraperitoneal DMDTC adm inistration, it does not appear to be involved in the response to loca l ovarian exposure. Moreover, the blockade in response to the diestrou s IB exposure likely involves two separate mechanisms, one attributabl e to an alteration in ovarian hormonal feedback to the brain (or pitui tary), inhibiting the LH surge, and the other associated with a direct , as yet undetermined, effect on local preovulatory events within the ovary. (C) 1997 Elsevier Science Inc.