An evaluation of the role of antiestrogen-binding sites in mediating the growth modulatory effects of antiestrogens: Studies using t-butylphenoxyethyl diethylamine, a compound lacking affinity for the estrogen receptor

Yhun Yhong Sheen, David M. Simpson, Benita S Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

Tert-butylphenoxyethyl diethylamine (BPEA), a compound synthesized by us, was designed to incorporate features important in binding to antiestrogen-binding sites (AEBS) while lacking features important in binding to the estrogen receptor (ER). With this compound, we have addressed the question of the role of AEBS in mediating the growth modulatory effects of antiestrogens. BPEA has an affinity for AEBS 6% that of tamoxifen and an affinity for ER less than 0.0003% that of estradiol. BPEA (10 −11 –10 −6 M) had no effect on the growth of MCF-7 breast cancer cells and no effect on inhibition of the growth of MCF-7 cells by different concentrations of the antiestrogen tamoxifen. In addition, BPEA (even at doses of 1 mg/day·50 g rat) exhibited no uterotropic or antiuterotropic activity in immature rats and had no influence on the agonistic or antagonistic activity of varying concentrations of tamoxifen on uterine weight. Hence, we conclude that occupancy of AEBS, at least by BPEA, does not modulate growth of the uterus or breast cancer cells and does not influence the potency of tamoxifen as an antiestrogen. These findings raise serious doubts about the role of the AEBS in mediating directly the growth modulatory effects of antiestrogens.

Original languageEnglish (US)
Pages (from-to)561-564
Number of pages4
JournalEndocrinology
Volume117
Issue number2
DOIs
StatePublished - Aug 1985

Fingerprint

Estrogen Receptor Modulators
Estrogen Receptors
Binding Sites
Growth
Tamoxifen
Breast Neoplasms
diethylamine
Uterine Neoplasms
MCF-7 Cells
Estradiol
Weights and Measures

ASJC Scopus subject areas

  • Endocrinology

Cite this

@article{29e8411890f5455c9c7d103c4c562b6a,
title = "An evaluation of the role of antiestrogen-binding sites in mediating the growth modulatory effects of antiestrogens: Studies using t-butylphenoxyethyl diethylamine, a compound lacking affinity for the estrogen receptor",
abstract = "Tert-butylphenoxyethyl diethylamine (BPEA), a compound synthesized by us, was designed to incorporate features important in binding to antiestrogen-binding sites (AEBS) while lacking features important in binding to the estrogen receptor (ER). With this compound, we have addressed the question of the role of AEBS in mediating the growth modulatory effects of antiestrogens. BPEA has an affinity for AEBS 6{\%} that of tamoxifen and an affinity for ER less than 0.0003{\%} that of estradiol. BPEA (10 −11 –10 −6 M) had no effect on the growth of MCF-7 breast cancer cells and no effect on inhibition of the growth of MCF-7 cells by different concentrations of the antiestrogen tamoxifen. In addition, BPEA (even at doses of 1 mg/day·50 g rat) exhibited no uterotropic or antiuterotropic activity in immature rats and had no influence on the agonistic or antagonistic activity of varying concentrations of tamoxifen on uterine weight. Hence, we conclude that occupancy of AEBS, at least by BPEA, does not modulate growth of the uterus or breast cancer cells and does not influence the potency of tamoxifen as an antiestrogen. These findings raise serious doubts about the role of the AEBS in mediating directly the growth modulatory effects of antiestrogens.",
author = "Sheen, {Yhun Yhong} and Simpson, {David M.} and Katzenellenbogen, {Benita S}",
year = "1985",
month = "8",
doi = "10.1210/endo-117-2-561",
language = "English (US)",
volume = "117",
pages = "561--564",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "2",

}

TY - JOUR

T1 - An evaluation of the role of antiestrogen-binding sites in mediating the growth modulatory effects of antiestrogens

T2 - Studies using t-butylphenoxyethyl diethylamine, a compound lacking affinity for the estrogen receptor

AU - Sheen, Yhun Yhong

AU - Simpson, David M.

AU - Katzenellenbogen, Benita S

PY - 1985/8

Y1 - 1985/8

N2 - Tert-butylphenoxyethyl diethylamine (BPEA), a compound synthesized by us, was designed to incorporate features important in binding to antiestrogen-binding sites (AEBS) while lacking features important in binding to the estrogen receptor (ER). With this compound, we have addressed the question of the role of AEBS in mediating the growth modulatory effects of antiestrogens. BPEA has an affinity for AEBS 6% that of tamoxifen and an affinity for ER less than 0.0003% that of estradiol. BPEA (10 −11 –10 −6 M) had no effect on the growth of MCF-7 breast cancer cells and no effect on inhibition of the growth of MCF-7 cells by different concentrations of the antiestrogen tamoxifen. In addition, BPEA (even at doses of 1 mg/day·50 g rat) exhibited no uterotropic or antiuterotropic activity in immature rats and had no influence on the agonistic or antagonistic activity of varying concentrations of tamoxifen on uterine weight. Hence, we conclude that occupancy of AEBS, at least by BPEA, does not modulate growth of the uterus or breast cancer cells and does not influence the potency of tamoxifen as an antiestrogen. These findings raise serious doubts about the role of the AEBS in mediating directly the growth modulatory effects of antiestrogens.

AB - Tert-butylphenoxyethyl diethylamine (BPEA), a compound synthesized by us, was designed to incorporate features important in binding to antiestrogen-binding sites (AEBS) while lacking features important in binding to the estrogen receptor (ER). With this compound, we have addressed the question of the role of AEBS in mediating the growth modulatory effects of antiestrogens. BPEA has an affinity for AEBS 6% that of tamoxifen and an affinity for ER less than 0.0003% that of estradiol. BPEA (10 −11 –10 −6 M) had no effect on the growth of MCF-7 breast cancer cells and no effect on inhibition of the growth of MCF-7 cells by different concentrations of the antiestrogen tamoxifen. In addition, BPEA (even at doses of 1 mg/day·50 g rat) exhibited no uterotropic or antiuterotropic activity in immature rats and had no influence on the agonistic or antagonistic activity of varying concentrations of tamoxifen on uterine weight. Hence, we conclude that occupancy of AEBS, at least by BPEA, does not modulate growth of the uterus or breast cancer cells and does not influence the potency of tamoxifen as an antiestrogen. These findings raise serious doubts about the role of the AEBS in mediating directly the growth modulatory effects of antiestrogens.

UR - http://www.scopus.com/inward/record.url?scp=0022415521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022415521&partnerID=8YFLogxK

U2 - 10.1210/endo-117-2-561

DO - 10.1210/endo-117-2-561

M3 - Article

C2 - 4017947

AN - SCOPUS:0022415521

VL - 117

SP - 561

EP - 564

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 2

ER -