The classical estrogen receptor transcriptional pathway: Implications in human osteoblasts

David G. Monroe, Frank J. Secreto, Sundeep Khosla, Thomas C. Spelsberg

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

This article is based on a presentation given at the Advances in Skeletal Anabolic Agents for the Treatment of Osteoporosis meeting. This meeting included an overview of advances in the genomic actions of estrogen (E2) in osteoblast (OB) cells, followed by recent studies in this laboratory. It has been well documented that E2 and selective estrogen receptor modulators (SERMs) serve as regulators of skeletal homeostasis and are the primary clinical therapies for the prevention of bone loss. E2 directly regulates selective gene expression and activity of OBs and osteoclasts (OCs) and indirectly regulates OB-OC coupling via specific paracrine factors. An overview with recent updates of the classical estrogen receptor (ER) genomic pathway is briefly described. This pathway involves E2 or SERM binding to the ER isoforms (ERα and ERβ), binding of the complex to target gene promoters, and the association of specific nuclear coregulators, which can either participate in the activation or inhibition of gene transcription. Other important recent advancements such as ligand-induced ER structural changes and the rapid interactions of receptors and coregulators with chromatin are also described. Studies in this laboratory have recently demonstrated ER isoform-specific actions of ERs on human OB gene expression and cell proliferation. In a U2OS osteoblastic cell model expressing ERα, ERβ, or both isoforms, specific patterns of E2-induced gene expression using gene microarrays are observed. The results of these studies raise interesting possibilities to the understanding of tissue- and disease-specific responses (including steroid resistance) and the use of selective ER isoform inhibitors/activators in steroid therapy. An ER isoform-specific interaction with coregulators could explain the isoform-specific gene regulation.

Original languageEnglish (US)
Pages (from-to)129-140
Number of pages12
JournalClinical Reviews in Bone and Mineral Metabolism
Volume4
Issue number2
DOIs
StatePublished - 2006

Keywords

  • Estrogen receptor
  • Microarray
  • Osteoblasts
  • Transcription

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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