Mechanism of the estrogen receptor interaction with 4-hydroxytamoxifen

Journal Article · Fri Apr 01 00:00:00 EST 1988 · Mol. Endocrinol.; (United States)

DOI:https://doi.org/10.1210/mend-2-4-307· OSTI ID:7140968

Sasson, S; Notides, A C

The binding mechanism of the estrogen receptor with 4-(/sup 3/H)hydroxytamoxifen was investigated. The equilibrium binding analysis with 4-(/sup 3/H)hydroxytamoxifen indicated a positive cooperative interaction: the Scatchard plot was convex and the Hill coefficient was 1.4-1.5. This binding appears similar to the positively cooperative interaction of the estrogen receptor with (/sup 3/H)estradiol. However, a competitive binding assay with a saturating concentration of (/sup 3/H) estradiol and variable concentrations of 4-hydroxytamoxifen produced nonparallel displacement curves indicating that the binding mechanism of the receptor with these two ligands is different. The competitive binding assay with (/sup 3/H)estradiol and 4-hydroxytamoxifen at constant molar ratios demonstrated that the receptor's affinity for estradiol was reduced and the receptor preferentially bound 4-hydroxytamoxifen. These data suggest that 4-hydroxytamoxifen interacts with the receptor differently than estradiol; it antagonizes the binding of estradiol when these two ligands are simultaneously present.

• Research Organization: Hebrew Univ. School of Medicine, Jerusalem (Israel)
• OSTI ID: 7140968
• Journal Information: Mol. Endocrinol.; (United States), Vol. 2:4
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ESTROGENS
RECEPTORS
BIOCHEMICAL REACTION KINETICS
CATTLE
CPB
ESTRADIOL
LIGANDS
TAMOXIFEN
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
DOMESTIC ANIMALS
ESTRANES
HORMONES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
REACTION KINETICS
RUMINANTS
STEROID HORMONES
STEROIDS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques