Middleton M C, Milne C M, Moreland S, Hasmall R L
Toxicol Appl Pharmacol. 1986 Apr;83(2):230-9. doi: 10.1016/0041-008x(86)90300-5.
When a single oral dose of 5 or 25 mg/kg of the substituted triazole R151885 [1,1-di(4-fluorophenyl)-2-(1,2,4-triazol-1-yl)-ethanol] was administered at midday on diestrus-2 to rats with regular 4-day estrous cycles, the subsequent ovulation was delayed by 24 or 48 hr, respectively. There was no evidence of toxicity at the doses used. The only morphological changes detected in the reproductive tract were a delay in accumulation of uterine fluid and prolonged but normal follicular maturation prior to the delayed ovulation. The delayed follicles were slightly larger than normal follicles at the time of ovulation. The preovulatory peak plasma concentrations of progesterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were delayed by 24 hr in rats treated with 5 mg/kg of R151885 on diestrus-2. Although there was a normal preovulatory peak plasma concentration of estradiol, values were reduced by between 30 to 50% late on diestrus-2 and early on proestrus. Additionally, in ovariectomized rats, 3 daily doses of 25 mg/kg of R151885 antagonized the action of estradiol on the uterus by 45%. We suggest that the reductions in plasma estradiol concentrations during diestrus-2 and proestrus, combined with some antagonism of estradiol's action, may prevent adequate priming of the pituitary thereby suppressing the preovulatory LH surge required for ovulation. The suppression of this LH surge is of a temporary nature indicating a reversible effect of R151885 on the hormonal control system.
在动情周期为4天的正常大鼠的动情后期-2中午，单次口服5或25 mg/kg的取代三唑R151885 [1,1-二(4-氟苯基)-2-(1,2,4-三唑-1-基)乙醇]，随后的排卵分别延迟24或48小时。在所使用的剂量下没有毒性证据。在生殖道中检测到的唯一形态学变化是子宫液积累延迟以及在延迟排卵前卵泡成熟延长但正常。延迟的卵泡在排卵时比正常卵泡略大。在动情后期-2用5 mg/kg的R151885处理的大鼠中，孕酮、促卵泡激素（FSH）和促黄体生成素（LH）的排卵前血浆峰值浓度延迟24小时。虽然雌二醇有正常的排卵前血浆峰值浓度，但在动情后期-2晚期和动情前期早期，其值降低了30%至50%。此外，在去卵巢大鼠中，连续3天每天给予25 mg/kg的R151885可使雌二醇对子宫的作用拮抗45%。我们认为，动情后期-2和动情前期血浆雌二醇浓度的降低，以及雌二醇作用的一些拮抗作用，可能会阻止垂体的充分启动，从而抑制排卵所需的排卵前LH峰。对该LH峰的抑制是暂时的，表明R151885对激素控制系统有可逆作用。
