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S A McCormack

Publications and source records attributed to S A McCormack.

44 records · Page 3Linked to original sources
PubMed1979

Mechanism of action of estrogen agonists and antagonists.

The relationship between estrogen agonists and antagonists and the nuclear binding of the estrogen receptor was investigated in the immature rat uterus. Estriol (and other short acting estrogens) are antagonistic when administered as a single injection due to the inability of the receptor-estriol complex to be retained by uterine nuclei for a critical period necessary to stimulate true uterine growth. This failure of the receptor-estriol complex to be retained appears to be due to rapid clearance of estriol from uterine tissue following a single injection of the hormone. When estriol is present in a chronic fashion, it acts as an agonist because receptor estriol complex is retained at nuclear sites for long periods of time. Nonsteroid estrogen antagonists, such as Nafoxidine, also cause long term nuclear retention of the estrogen receptor and act as estrogen agonists after a single injection. However, after multiple injections these drugs are antagonistic and this effect is correlated with decrease availability of cytoplasmic estrogen receptors. In addition, these compounds appear to specifically stimulate the growth of uterine epithelial cells while minimally affecting other cell types which results in hyperestrogenization of the epithelium.

Animals↗
PubMed1976

A high-affinity estrogen-binding protein in rat placental trophoblast.

A high-affinity, low-capacity estradiol-binding molecule (RE) has been demonstrated in the basal zone trophoblast (BZT) of the pregnant rat. On day 11 of pregnancy (day 0 = first sperm-positive day) RE is present in BZT cytosol, where it has a ka of 1.2 X 10(6)M-1 sec-1, t1/2 = 12.7 min, at 20 C. The Kd, under similar conditions, consists of 2 components, 1.3 X 10(-4) sec-1, t1/2 = 90 min, and 5.9 X 10(-5) sec-1, t1/2 = 196 min. When one uses the faster component, the equilibrium constant, Kd, obtained from kd/ka is 1.1 X 10(-10)M, in close agreement with that obtained from Scatchard analysis of specific estradiol (E2) binding at 20 C. On day 11 there were approximately 12,000 sites/cell in BZT cytosol. Scatchard analysis of nuclear RE on day 11 indicated a Kd of 1.85 X 10(-10)M and approximately 21,000 sites/nucleus, but, in day 15 BZT, nuclear RE was undetectable. Neither cytosol nor nuclei prepared from placental labyrinthine zone (LZT) tissue (fetal placenta) showed evidence of high-affinity, low-capacity E2 binding. Sucrose density gradient analysis on 5-20% linear gradients showed the cytosol RE to be approximately 4S whether in high or low-salt conditions. When measured against binding by 3H-labeled estradiol (*E2), the cytosol BTZ RE was competed for strongly (80-90%) by estrone, estriol, diethylstilbestrol, and estradiol-17alpha at 200 times excess. Nafoxidine-HCl, also at 200X excess, competed to approximately 50%. Corticosterone, progesterone, testosterone, dehydroepiandrosterone, and pregnenolone did not compete. The hormone specificity of nuclear BZT RE was similar to that of the comparable cytosol RE with the exception that nafoxidine did not compete. This was probably due to differences in kinetics, nafoxidine requiring a longer time to reach equilibrium than the other estrogens. The size of the nuclear RE by sucrose density gradient analysis was approximately 2S by KCl extraction (which was inefficient) or 4S by trypsin extraction. We conclude that the BZT of the day-11 rat placenta contains an estrogen-binding molecule with many of the attributes of a true receptor.

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