Zearalenones: Characterization of the estrogenic potencies and receptor interactions of a series of fungal β-resorcylic acid lactones

Benita S Katzenellenbogen, John A. Katzenellenbogen, David Mordecai

Research output: Contribution to journalArticle

Abstract

This study investigates the direct estrogen receptor interactions and the character of the biological activities of three estrogenic resorcylic acid lactones in the immature rat uterus. These compounds are fungal metabolites (P-1492; zearalenone) or derivatives thereof (P-1496 and P-1560; epimeric zearalanols) that have been associated with estrogenizing syndromes in cattle fed mold-infected grain. The compounds compete with estradiol for binding to the cytoplasmic receptor (P- 1496, 13.6%; P-1492, 1.8%; P-1560, 0.8% that of estradiol), and they translocate estrogen receptor sites to the nucleus, with P- 1496 showing the most prolonged nuclear receptor interaction. The three compounds induce the synthesis of the uterine induced protein (P-1496 > P-1560 > P-1492) and increase uterine weight. Direct binding studies with the most potent compound P-1496, in tritium-labeled form indicates a Kd of 1.8 nM (compared to 0.12 nM for estradiol) for interaction with uterine cytoplasmic receptor. Cytoplasmic receptor complexes with [3H]P-1496 sediment at 8S on low salt sucrose density gradients, as do [ HJestradiol receptor complexes. After uterine uptake of [3H]P-1496, salt-extracted nuclear receptor complexes sediment at 5.4S on 0.4 M KC1 sucrose density gradients, as do the nuclear [3H]estradiol receptor complexes. These studies document that despite the unique chemical nature of these resorcylic acid lactones, they interact directly with the estrogen receptor and evoke many of the same biological and biochemical responses that are evoked by the natural estrogen estradiol.

Original languageEnglish (US)
Pages (from-to)33-40
Number of pages8
JournalEndocrinology
Volume105
Issue number1
DOIs
StatePublished - Jul 1979

Fingerprint

Zeranol
Zearalenone
Lactones
Cytoplasmic and Nuclear Receptors
Acids
Estradiol
Estrogen Receptors
Sucrose
Salts
Estradiol Receptors
Tritium
Uterus
Estrogens
Fungi
Weights and Measures

ASJC Scopus subject areas

  • Endocrinology

Cite this

Zearalenones : Characterization of the estrogenic potencies and receptor interactions of a series of fungal β-resorcylic acid lactones. / Katzenellenbogen, Benita S; Katzenellenbogen, John A.; Mordecai, David.

In: Endocrinology, Vol. 105, No. 1, 07.1979, p. 33-40.

Research output: Contribution to journalArticle

@article{1a6aa9ea0a6c4549b32fb663191bc877,
title = "Zearalenones: Characterization of the estrogenic potencies and receptor interactions of a series of fungal β-resorcylic acid lactones",
abstract = "This study investigates the direct estrogen receptor interactions and the character of the biological activities of three estrogenic resorcylic acid lactones in the immature rat uterus. These compounds are fungal metabolites (P-1492; zearalenone) or derivatives thereof (P-1496 and P-1560; epimeric zearalanols) that have been associated with estrogenizing syndromes in cattle fed mold-infected grain. The compounds compete with estradiol for binding to the cytoplasmic receptor (P- 1496, 13.6{\%}; P-1492, 1.8{\%}; P-1560, 0.8{\%} that of estradiol), and they translocate estrogen receptor sites to the nucleus, with P- 1496 showing the most prolonged nuclear receptor interaction. The three compounds induce the synthesis of the uterine induced protein (P-1496 > P-1560 > P-1492) and increase uterine weight. Direct binding studies with the most potent compound P-1496, in tritium-labeled form indicates a Kd of 1.8 nM (compared to 0.12 nM for estradiol) for interaction with uterine cytoplasmic receptor. Cytoplasmic receptor complexes with [3H]P-1496 sediment at 8S on low salt sucrose density gradients, as do [ HJestradiol receptor complexes. After uterine uptake of [3H]P-1496, salt-extracted nuclear receptor complexes sediment at 5.4S on 0.4 M KC1 sucrose density gradients, as do the nuclear [3H]estradiol receptor complexes. These studies document that despite the unique chemical nature of these resorcylic acid lactones, they interact directly with the estrogen receptor and evoke many of the same biological and biochemical responses that are evoked by the natural estrogen estradiol.",
author = "Katzenellenbogen, {Benita S} and Katzenellenbogen, {John A.} and David Mordecai",
year = "1979",
month = "7",
doi = "10.1210/endo-105-1-33",
language = "English (US)",
volume = "105",
pages = "33--40",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Zearalenones

T2 - Characterization of the estrogenic potencies and receptor interactions of a series of fungal β-resorcylic acid lactones

AU - Katzenellenbogen, Benita S

AU - Katzenellenbogen, John A.

AU - Mordecai, David

PY - 1979/7

Y1 - 1979/7

N2 - This study investigates the direct estrogen receptor interactions and the character of the biological activities of three estrogenic resorcylic acid lactones in the immature rat uterus. These compounds are fungal metabolites (P-1492; zearalenone) or derivatives thereof (P-1496 and P-1560; epimeric zearalanols) that have been associated with estrogenizing syndromes in cattle fed mold-infected grain. The compounds compete with estradiol for binding to the cytoplasmic receptor (P- 1496, 13.6%; P-1492, 1.8%; P-1560, 0.8% that of estradiol), and they translocate estrogen receptor sites to the nucleus, with P- 1496 showing the most prolonged nuclear receptor interaction. The three compounds induce the synthesis of the uterine induced protein (P-1496 > P-1560 > P-1492) and increase uterine weight. Direct binding studies with the most potent compound P-1496, in tritium-labeled form indicates a Kd of 1.8 nM (compared to 0.12 nM for estradiol) for interaction with uterine cytoplasmic receptor. Cytoplasmic receptor complexes with [3H]P-1496 sediment at 8S on low salt sucrose density gradients, as do [ HJestradiol receptor complexes. After uterine uptake of [3H]P-1496, salt-extracted nuclear receptor complexes sediment at 5.4S on 0.4 M KC1 sucrose density gradients, as do the nuclear [3H]estradiol receptor complexes. These studies document that despite the unique chemical nature of these resorcylic acid lactones, they interact directly with the estrogen receptor and evoke many of the same biological and biochemical responses that are evoked by the natural estrogen estradiol.

AB - This study investigates the direct estrogen receptor interactions and the character of the biological activities of three estrogenic resorcylic acid lactones in the immature rat uterus. These compounds are fungal metabolites (P-1492; zearalenone) or derivatives thereof (P-1496 and P-1560; epimeric zearalanols) that have been associated with estrogenizing syndromes in cattle fed mold-infected grain. The compounds compete with estradiol for binding to the cytoplasmic receptor (P- 1496, 13.6%; P-1492, 1.8%; P-1560, 0.8% that of estradiol), and they translocate estrogen receptor sites to the nucleus, with P- 1496 showing the most prolonged nuclear receptor interaction. The three compounds induce the synthesis of the uterine induced protein (P-1496 > P-1560 > P-1492) and increase uterine weight. Direct binding studies with the most potent compound P-1496, in tritium-labeled form indicates a Kd of 1.8 nM (compared to 0.12 nM for estradiol) for interaction with uterine cytoplasmic receptor. Cytoplasmic receptor complexes with [3H]P-1496 sediment at 8S on low salt sucrose density gradients, as do [ HJestradiol receptor complexes. After uterine uptake of [3H]P-1496, salt-extracted nuclear receptor complexes sediment at 5.4S on 0.4 M KC1 sucrose density gradients, as do the nuclear [3H]estradiol receptor complexes. These studies document that despite the unique chemical nature of these resorcylic acid lactones, they interact directly with the estrogen receptor and evoke many of the same biological and biochemical responses that are evoked by the natural estrogen estradiol.

UR - http://www.scopus.com/inward/record.url?scp=0018749247&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018749247&partnerID=8YFLogxK

U2 - 10.1210/endo-105-1-33

DO - 10.1210/endo-105-1-33

M3 - Article

C2 - 446414

AN - SCOPUS:0018749247

VL - 105

SP - 33

EP - 40

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 1

ER -