Effects of a Single Injection of an Estrogen Antagonist on the Estrous Cycle of the Rat1

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Abstract
Ovariectomy of rats with 4- or 5-day estrous cycles at 1600 hr. on the day before pro-estrus but not at 1000 hr. on the morning of proestrus blocks vaginal cornification and mating. When performed at 1000 hr. on the day prior to proestrus, ovariectomy also blocks the proestrous uterine weight increase and the drop in pituitary LH [leuteinizing hormone]. A single injection of MER-25 [l-(p-diethylaminoethoxyphenyl)-l-phenyl-2-p-methoxyphenyl ethanol], a nonsteroidal estrogen antagonist, was given at specific times in the estrous cycle to investigate whether the responses blocked by ovariectomy might be attributed entirely to a loss of estrogen secretion at critical times. In general, MER-25 administered in a single injection of 20 mg blocked vaginal cornification and the proestrous uterine ballooning as ovariectomy does, but did not completely prevent mating behavior or ovulation; MER-25 induced higher than control levels of pituitary LH content as estrus even in the presence of ovulatory evidence of LH release in some rats. When the dosage was increased to 40 mg, there was virtually complete inhibition of ovulation, and mating as well. The rats with 4-day cycles differed from those with 5-day cycles in 3 respects after treatment. MER-25, when given on the afternoon before proestrus, blocked vaginal cornification in 5-day cyclers but not in 4-day cyclers. There was also a significantly greater inhibition of ovulation in 4-day cyclers. The 4-day cyclers showed higher pituitary LH contents at estrus than the 5-day cyclers.

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