Li X, Johnson D C, Rozman K K
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160, USA.
Toxicol Appl Pharmacol. 1995 Aug;133(2):321-7. doi: 10.1006/taap.1995.1157.
A previous study has shown that exposure of adult rats to TCDD alters estrous cyclicity and ovulation. To further explore the mechanisms involved we employed the gonadotropin-primed immature female rat model. Single doses (0.3-60 micrograms/kg) of TCDD, dissolved in corn oil, were given orally to 22-day-old rats. Equine chorionic gonadotropin (eCG) (20 IU) was injected 24 hr later to induce follicular development. Rats were killed at various times after eCG, blood was collected, and ovarian weights were obtained. Serum concentrations of estradiol-17 beta (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (LTH) were measured by radioimmunoassay. Ovulation was determined 72 hr after injection of eCG by counting ova flushed from oviducts. TCDD reduced dose-dependently the increase in ovarian weight gain induced by eCG and also decreased the number of animals ovulating as well as the number of ova recovered; the ED50 was between 3 and 10 micrograms/kg of TCDD. The increase in serum E2 induced by eCG was enhanced in animals treated with TCDD. Peak serum levels of FSH and LH, but not of LTH, were decreased by TCDD. E2, as expected, decreased dramatically in control animals between 60 and 72 hr after injection of eCG, concomitant with a preovulatory surge in LH. This response was absent in TCDD-treated animals. None of these effects were related to decreased food consumption since they were absent in pair-fed controls. In hypophysectomized immature rats treated with eCG and exogenous LH the percentage of rats ovulating and the number of ova recovered were also significantly reduced by TCDD (10 and 60 micrograms/kg). These results suggest that TCDD alters reproductive function in the immature female rat model via effects on the hypothalamic-pituitary axis as well as by direct effects on the ovary.
先前的一项研究表明，成年大鼠接触2,3,7,8-四氯二苯并对二恶英（TCDD）会改变发情周期和排卵。为了进一步探究其中涉及的机制，我们采用了促性腺激素预处理的未成熟雌性大鼠模型。将溶解于玉米油中的单剂量（0.3 - 60微克/千克）TCDD经口给予22日龄大鼠。24小时后注射马绒毛膜促性腺激素（eCG）（20国际单位）以诱导卵泡发育。在注射eCG后的不同时间点处死大鼠，采集血液并获取卵巢重量。采用放射免疫分析法测定血清中雌二醇-17β（E2）、促黄体生成素（LH）、促卵泡生成素（FSH）和催乳素（LTH）的浓度。在注射eCG 72小时后，通过计算从输卵管中冲出的卵子数量来确定排卵情况。TCDD剂量依赖性地降低了eCG诱导的卵巢重量增加，同时也减少了排卵动物的数量以及回收的卵子数量；TCDD的半数有效剂量（ED50）在3至10微克/千克之间。在接受TCDD处理的动物中，eCG诱导的血清E2升高得到增强。TCDD降低了FSH和LH的血清峰值水平，但未降低LTH的血清峰值水平。正如预期的那样，在注射eCG后60至72小时之间，对照动物的E2急剧下降，同时伴随着LH的排卵前激增。在接受TCDD处理的动物中未出现这种反应。这些效应均与食物摄入量减少无关，因为在配对喂养的对照动物中未出现这些效应。在用eCG和外源性LH处理的垂体切除未成熟大鼠中，TCDD（10和60微克/千克）也显著降低了排卵大鼠的百分比和回收的卵子数量。这些结果表明，TCDD通过影响下丘脑 - 垂体轴以及直接作用于卵巢，改变了未成熟雌性大鼠模型的生殖功能。
