Blockade of ovulation in the rat by systemic and ovarian intrabursal administration of the fungicide sodium dimethyldithiocarbamate.
Dithiocarbamates, acting as inhibitors of catecholamine synthesis, have been reported to block ovulation in female rats following systemic administration by suppressing the neural noradrenergic signaling involved in triggering the ovulatory surge of luteinizing hormone. The ovaries 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 experiments investigated whether the dithiocarbamate fungicide dimethyldithiocarbamate (DMDTC) would block oocyte release in normally cycling rats 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 effects appear to be mediated through different mechanisms. The unilateral IB injections were effective only on the exposed side for each ovarian pair, while no alterations were seen in ovarian norepinephrine. IB administration 24 h earlier blocked ovulation on both sides, while hCG injections were able to restore ovulation on the noninjected side only, implying that diestrous DMDTC was inhibiting the LH surge. The data indicate that while an effect on hypothalamic catecholamine synthesis may underlie the ovulatory blockade following intraperitoneal DMDTC administration, it does not appear to be involved in the response to local ovarian exposure. Moreover, the blockade in response to the diestrous IB exposure likely involves two separate mechanisms, one attributable to an alteration in ovarian hormonal feedback to the brain (or pituitary), inhibiting the LH surge, and the other associated with a direct, as yet undetermined, effect on local preovulatory events within the ovary.
Goldman
J M
JM
Endocrinology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Parrish
M B
MB
Cooper
R L
RL
McElroy
W K
WK
D000818:Animals; D004125:Dimethyldithiocarbamate / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D009638:Norepinephrine / Q000378:metabolism; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects*; D011359:Proestrus; D051381:Rats
D004125:Dimethyldithiocarbamate; D005659:Fungicides, Industrial; D009638:Norepinephrine