Nonsteroidal Estrogen Antagonist Research Articles

Displacement of 17-beta-estradiol from uterine receptor sites by an estrogen antagonist.

SummaryA potent nonsteroidal estrogen antagonist (CN-55,945-27) was found to displace previously bound radioactive 17β-estradiol from the uterus when added to an incubation medium containing uterine horns obtained from intact rats or when administered by gavage to ovariectomized rats. In vitro, this phenomenon was indicated by a significant decrease in the uterine estradiol-4-14C with a concomitant and progressive increase in the level of radioactivity within the medium during a 3-hour incubation period. Similar results were obtained in vitro when nonradioactive 17β-estradiol was incubated with uteri obtained from rats previously treated with 17β-estradiol-4-14C in vivo. When CN-55,945-27 was given orally to rats injected subcutaneously 6 hours previously with 17β-estradiol-6,7-3H, it markedly increased the rate of release of estradiol from the uterus over that observed in animals receiving oral vehicle. This effect, as shown by a decrease in uterine estradiol, was significant within 2 hours, increased ma...

Effects of a single injection of an estrogen antagonist on the estrous cycle of the rat.

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)

Action of an estrogen antagonist on the electrical and mechanical properties of the rat uterus in vitro.

Membrane potentials and isometric contractions were recorded simultaneously from myometrial strips isolated from rats either parturient or on the final day of gestation. The nonsteroidal estrogen antagonist, CN-55, 945-27, inhibited spontaneous contractions as well as those elicited by oxytocin, acetylcholine and electrical field stimulation. Accompanying these changes in contractile force were a reduction in the height and rising velocity of the action potentials and a decrease in the frequency of action potentials discharged during each contraction. CN did not alter the level of the resting membrane potential. These membrane electrical effects suggested that CN interfered with the initiation and propagation of action potentials over the muscle, thereby reducing the number of muscle fibers activated during each contraction and thus the force of contraction. In addition to the effects on the excitable membrane which would indirectly alter the magnitude of contraction, CN also acted directly on the contrac...

EFFECT OF ESTRADIOL AND ETHAMOXYTRIPHETOL (MER-25) ON THE MOUSE UTERUS.

A nonsteroidal estrogen antagonist, ethamoxytriphetol (MER-25), was shown to have some inherent estrogenicstimulating potency on alkaline phosphatase and isocitric dehydrogenase systems and uterine weight gain in mice. It was also shown to inhibit the increases in enzyme activities stimulated with estradiol benzoate. (Endocrinology76: 127, 1965)

Chemical Induction of Ovulation

To the Editor:— The lead article ( JAMA 178 :101 [Oct. 14] 1961) by Greenblatt and his associates called forth an excellent editorial entitled Induction of Ovulation with MRL/41. Two synthetic nonsteroidal drugs, 1-[p-2-diethylaminoethoxyphenyl]-1-2-p-methoxyphenlyethanol (MER-25) and clomiphene citrate (MRL/41), both structurally related to chlorotrianisene (Tace) but without that compound's estrogenic activity, have been observed to produce ovulatory menstrual cycles in certain types of ammenorrhea. Three groups of investigators have now reported this observation: Tyler, Olson, and Gotlib in 1960; Kistner and Smith in 1960, and again in 1961; and, finally Greenblatt and his associates. One of these reports was not referred to, either in the editorial or in the paper by Green-blatt et al., for which reason I will give the complete reference (Kistner, R. W., and Smith, O. W.: Observations on Use of a Non-Steroidal Estrogen Antagonist: MER-25, Surg Forum 10 :725, 1960). I would like to call especial attention

Observations on the use of a nonsteroidal estrogen antagonist: I. Cystic disease of the breast

Observations on the use of a nonsteroidal estrogen antagonist: I. Cystic disease of the breast