INTERACTION OF RING-B UNSATURATED ESTROGENS WITH ESTROGEN-RECEPTORS OF HUMAN ENDOMETRIUM AND RAT UTERUS

被引：50

作者：

BHAVNANI, BR

WOOLEVER, CA

机构：

[1] Department of Obstetrics and Gynecology, St. Michael's Hospital, University of Toronto, Toronto, Ont.

来源：

STEROIDS | 1991年 / 56卷 / 04期

基金：

英国医学研究理事会;

关键词：

UTEROTROPIC ACTIVITY; EQUINE ESTROGENS; RING-B UNSATURATED ESTROGENS; ESTROGEN RECEPTORS; ESTROGEN BIOASSAY; ENDOMETRIAL CANCER; EQUILIN; 17-BETA-DIHYDROEQUILIN;

D O I：

10.1016/0039-128X(91)90083-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The present investigation was undertaken to compare the binding affinities (Ka) of the ring B unsaturated equine estrogens (equilin [Eq], equilenin [Eqn], 17-beta-dihydroequilin [17-beta-Eq], 17-beta-dihydroequilenin [17-beta-Eqn], 17-alpha-dihydroequilin [17-alpha-Eq], and 17-alpha-dihydroequilenin [17-alpha-Eqn]) and the classic estrogens (estrone [E1], 17-beta-estradiol [17-beta-E2], and 17-alpha-estradiol [17-alpha-E2]) for estrogen receptors in human endometrium and rat uterus. In both species, the ring B unsaturated estrogens bind with cytosol and nuclear receptors with high affinity (Ka x 10(9) M-1). The relative binding affinities of these estrogens were measured by determining the amount of unlabeled estrogen required to reduce by 50% the specific binding of [H-3]17-beta-Eq to endometrial cytosol receptors. The order of activity found was 17-beta-Eq > 17-beta-E2 > 17-beta-Eqn > E1 > Eq > 17-alpha-Eq > 17-alpha-E2 > 17-alpha-Eqn > Eqn. Essentially the same order of activity was observed when the apparent affinity constants of these estrogens for human and rat cytosol and nuclear receptors were determined by a competitive (inhibition) binding assay. Sucrose density gradient analysis indicated that these estrogens from protein complexes with cytosol and nuclear preparation that sediment at approximately 8S and 4S, respectively. The affinity constants for 17-beta-Eq were approximately two- to six-fold higher than E2 in both species. In a rat uterotropic assay, all nine estrogens were uterotropic. These data indicate that all ring B unsaturated estrogens present in conjugated equine estrogen preparations are biologically active and they express their biologic effects in the human endometrium by mechanisms similar to those described for the classic estrogens.

引用

页码：201 / 210

页数：10

共 40 条

[1] Smith, Prentice, Thompson, Herrman, Association of exogenous estrogens and endometrial carcinoma, N Engl J Med, 293, pp. 1164-1166, (1975)
[2] Ziel, Finkle, Increased risk of endometrial carcinoma among users of conjugated estrogens, N Engl J Med, 293, pp. 1167-1170, (1975)
[3] Buring, Bain, Ehrman, Conjugated estrogen use and risk of endometrial cancer, Am J Epidemiol, 124, pp. 434-441, (1986)
[4] Whitehead, Prevention of endometrial abnormalities, Acta Obstetricia et Gynecologica Scandinavica, 134, pp. 81-91, (1986)
[5] Evans, Hahnel, Distribution of estrogen receptors in cell fractions of human uterine tissue, J Endocrinol, 56, pp. 503-528, (1973)
[6] Bayard, Damilano, Robel, Baulieu, Cytoplasmic and nuclear estradiol and progesterone receptors in human endometrium, J Clin Endocrinol Metab, 46, pp. 635-648, (1978)
[7] Katzenellenbogen, Lam, Rutledge, Estrogen receptors of human endometrium: characterization of nuclear and cytoplasmic forms and comparisons with rat uterine receptors, J Steroid Biochem, 13, pp. 113-122, (1980)
[8] King, Dyer, Collins, Whitehead, Intracellular estradiol, estrone and estrogen receptor levels in endometria from postmenopausal women receiving estrogens and progestins, J Steroid Biochem, 13, pp. 377-382, (1980)
[9] Robel, Mortel, Baulieu, Estradioland progesterone receptors in human endometrium, Biochemical Actions of Hormones, 8, pp. 494-514, (1981)
[10] Mortel, Satyaswaroop, Clarke, Zaino, Sex steroid receptors in normal and malignant endometrium, Ann Pathol, 6, pp. 109-114, (1986)

← 1 2 3 4 →