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

Abstract

As previously demonstrated, ovariectomy of rats with 4-or 5-day estrous cycles at 1600 hr on the day before proestrus 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. A single injection of MER-25, 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 at 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. Finally, the 4-day cyclers showed higher pituitary LH contents at estrus than the 5-day cyclers. (Endocrinology 82: 959, 1968)

Changes in α-estradiol receptor and progesterone receptor expression in the locus coeruleus and preoptic area throughout the rat estrous cycle

“…Although basal estradiol levels were observed on metestrus and diestrus days, the expression of both receptors was lower on metestrus and increased gradually until reaching its maximum level at 16 h of diestrus afternoon. Increased levels of estradiol are required to activate the LH surge on proestrus afternoon since administration of estradiol inhibitors (Shirley et al 1968) and estradiol antiserum (Neill et al 1971) on diestrus blocks the proestrus LH surge. In this regard, this increase in the number of ER-ir cells in LC may be a way to prepare this nucleus to respond to the increase of estradiol levels which starts in the late evening of diestrus (Smith et al 1975) in order to activate the LH surge on proestrus afternoon, which was observed at 16 h in our study.…”

Luteinizing hormone-releasing hormone neurons express Fos protein during the proestrous surge of luteinizing hormone.

“…In the immature female rat, induction of an LH surge by exogenous steroid administration induces Fos expression in LHRH neurons (20). The dependence of the natural LH surge on gonadal steroids (21) strongly suggests that LHRH neurons would similarly express Fos at the time of the LH surge on the day of proestrus. Thus, in the present study, we used Fos expression to identify the neurons activated during the preovulatory LH surge as a means of defining the population of LHRH neurons that stimulate the LH surge.…”

Importance of Pituitary and Neural Actions of Estradiol in Induction of the Luteinizing Hormone Surge in the Ewe

“…The GnRH signal elicited high-amplitude surges of LH only in the presence of a peak estradiol concentration. Our findings are consistent with the conclusion that two actions are required for a rise in estradiol to elicit a full-amplitude surge of LH in the ewe: an action on the brain to evoke a sudden increase in GnRH release and an action on the pituitary to maximize its response to GnRH.Although it has long been recognized that a rise in circu lating estradiol induces the preovulatory discharge of lu teinizing hormone (LH) in spontaneously ovulating mam mals, the sites and mechanisms through which estradiol acts have been the subject of considerable debate [10,16,17,29,47,51]. On the one hand, increased gonadotropin-releasing hormone (GnRH) secretion during the LH surge has been suggested in the monkey [32,36], rat [43] and sheep [5,6,45], and certainly would seem an important mode of action for estradiol.…”