Cited by 364Estrogen and related hormone effectsEffects and risks of endocrine disrupting chemicalsPhytoestrogen effects and research

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Characterization of the Biological Roles of the Estrogen Receptors, ERα and ERβ, in Estrogen Target Tissues in Vivo through the Use of an ERα-Selective Ligand

Harris, Heather A., Katzenellenbogen, John A., Katzenellenbogen, Benita S.·2002·Endocrinology

DOI 10.1210/en.2002-220403

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Abstract

Estrogens elicit many biomedically important responses in different target tissues, and the respective roles of the two estrogen receptors, ERalpha and ERbeta, in mediating these bioactivities is incompletely understood. In this study, we investigated the activity of an ERalpha-selective agonist ligand, propyl pyrazole triol (PPT), in several rat animal models to define the involvement of ERalpha in these biological responses. In a short-term (4 d) uterotrophic assay, PPT was found to be as efficacious as 17alpha-ethinyl-17beta-estradiol in stimulating uterine weight gain and up-regulating complement 3 gene expression. In a 6-wk chronic model, PPT completely prevented the ovariectomy-induced body weight increase and loss of bone mineral density. It also increased uterine weight and markedly reduced plasma cholesterol levels in these mature animals. PPT was also effective in the brain. It increased progesterone receptor mRNA in the arcuate and ventromedial nuclei of the hypothalamus and prevented experimentally induced hot flushes. Our findings indicate that several physiologically relevant estrogen-induced tissue responses can be effectively evoked via ERalpha alone. By providing an approach that is complementary to that of analyzing the phenotype and response of ER knockout animals, our findings also demonstrate that ER subtype-selective ligands can play a valuable role in enhancing our understanding of how estrogens work through the two ER subtypes.

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Authors: Harris, H. A., Katzenellenbogen, J. A., & Katzenellenbogen, B. S.
Affiliations: Wyeth (US)
University of Illinois Urbana-Champaign (US)
Corresponding author: Katzenellenbogen, Benita S.
ORCID: Harris, Heather A.
Katzenellenbogen, John A.
Katzenellenbogen, Benita S.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2002-11
Volume: 143
Issue: 11
Pages: 4172-4177
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2002-220403
OpenAlex: W2011735277
Cited by: 357
References: 21
Citations by year: 2026: 1 · 2024: 13 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 7 · 2015: 12 · 2014: 12 · 2013: 19 · 2012: 16
FWCI: 13.15
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (R01CA018119)
National Institute of Diabetes and Digestive and Kidney Diseases (R37DK015556)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Health Sciences › Nursing › Nutrition and Dietetics › Phytoestrogen effects and research
Keywords: estrogen receptor alpha, estrogen receptor beta, propyl pyrazole triol, uterotrophic assay, uterine growth, bone mineral density, ovariectomy, serum cholesterol, progesterone receptor, hypothalamus, hot flashes, estrogen target tissues
MeSH terms: Animals, Body Weight, Complement C3, Estrogens, Ethinyl Estradiol, Female, Hypothalamus, Ligands, Organ Size, Ovariectomy, Phenols, Pyrazoles, Receptors, Estrogen, Receptors, Progesterone, RNA, Messenger, Skin Temperature, Uterus, Bone Density, Gene Expression, Rats, Sprague-Dawley, Estrogen Receptor alpha, Estrogen Receptor beta, Rats

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Characterization of the Biological Roles of the Estrogen Receptors, ERα and ERβ, in Estrogen Target Tissues in Vivo through the Use of an ERα-Selective Ligand

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