Goldman J M, Parrish M B, Cooper R L, McElroy W K
Endocrinology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Reprod Toxicol. 1997 Mar-Jun;11(2-3):185-90. doi: 10.1016/s0890-6238(97)00005-1.
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.
二硫代氨基甲酸盐作为儿茶酚胺合成的抑制剂，据报道，通过抑制参与触发促黄体生成素排卵高峰的神经去甲肾上腺素能信号，全身给药后可阻断雌性大鼠的排卵。卵巢也能合成去甲肾上腺素，并通过交感神经支配接受去甲肾上腺素能输入，有人认为这种输入可能在卵泡成熟和排卵中起作用。目前的实验研究了在动情前期促性腺激素释放激素高峰前全身给药时，二硫代氨基甲酸盐类杀菌剂二甲基二硫代氨基甲酸盐（DMDTC）是否会阻断正常发情周期大鼠的卵母细胞释放，如果是，该化合物在阴道动情前期当天晚些时候对一侧卵巢进行局部囊内暴露时，是否也会对排卵产生类似的直接卵巢效应。结果表明，腹腔注射和囊内注射均出现了与剂量相关的卵母细胞释放抑制。但这些作用似乎是通过不同机制介导的。单侧囊内注射仅对每对卵巢的暴露侧有效，而卵巢去甲肾上腺素未见改变。提前24小时进行囊内给药可阻断两侧排卵，而注射人绒毛膜促性腺激素仅能恢复未注射侧的排卵，这意味着动情后期的DMDTC抑制了促黄体生成素高峰。数据表明，虽然腹腔注射DMDTC后对下丘脑儿茶酚胺合成的影响可能是排卵阻断的基础，但它似乎不参与对局部卵巢暴露的反应。此外，动情后期囊内暴露引起的阻断可能涉及两种不同的机制，一种是由于卵巢对大脑（或垂体）的激素反馈改变，抑制了促黄体生成素高峰，另一种是对卵巢内局部排卵前事件产生直接但尚未确定的影响。
