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

Heather A. Harris, John A. Katzenellenbogen, Benita S. Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

Estrogens elicit many biomedically important responses in different target tissues, and the respective roles of the two estrogen receptors, ERα and ERβ, in mediating these bioactivities is incompletely understood. In this study, we investigated the activity of an ERα-selective agonist ligand, propyl pyrazole triol (PPT), in several rat animal models to define the involvement of ERα in these biological responses. In a shortterm (4 d) uterotrophic assay, PPT was found to be as efficacious as 17α-ethinyl-17β-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 ERα 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.

Original languageEnglish (US)
Pages (from-to)4172-4177
Number of pages6
JournalEndocrinology
Volume143
Issue number11
DOIs
StatePublished - Nov 1 2002

Fingerprint

Estrogen Receptors
Estrogens
Ligands
Arcuate Nucleus of Hypothalamus
Complement C3
Ethinyl Estradiol
Ovariectomy
Progesterone Receptors
Bone Density
Weight Gain
Weight Loss
Animal Models
Cholesterol
Body Weight
Phenotype
Gene Expression
Weights and Measures
Messenger RNA
1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole
Brain

ASJC Scopus subject areas

  • Endocrinology

Cite this

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.

In: Endocrinology, Vol. 143, No. 11, 01.11.2002, p. 4172-4177.

Research output: Contribution to journalArticle

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