Lab Anim Res.  2012 Jun;28(2):71-76. 10.5625/lar.2012.28.2.71.

Functions and physiological roles of two types of estrogen receptors, ERalpha and ERbeta, identified by estrogen receptor knockout mouse

• Lee HR
• Kim TH
• Choi KC

• KMID: 1436696
• DOI: http://doi.org/10.5625/lar.2012.28.2.71

Abstract

Estrogens, a class of steroid hormones, regulate the growth, development, and physiology of the human reproductive system. Estrogens also involve in the neuroendocrine, skeletal, adipogenesis, and cardiovascular systems. Estrogen signaling pathways are selectively stimulated or inhibited depending on a balance between the activities of estrogen receptor (ER) alpha or ERbeta in target organs. ERs belong to the steroid hormone superfamily of nuclear receptors, which act as transcription factors after binding to estrogen. The gene expression regulation by ERs is to modulate biological activities, such as reproductive organ development, bone modeling, cardiovascular system functioning, metabolism, and behavior in both females and males. Understanding of the general physiological roles of ERs has been gained when estrogen levels were ablated by ovariectomy and then replenished by treatment with exogenous estrogen. This technique is not sufficient to fully determine the exact function of estrogen signaling in general processes in living tissues. However, a transgenic mouse model has been useful to study gene-specific functions. ERalpha and ERbeta have different biological functions, and knockout and transgenic animal models have distinct phenotypes. Analysis of ERalpha and ERbeta function using knockout mouse models has identified the roles of estrogen signaling in general physiologic processes. Although transgenic mouse models do not always produce consistent results, they are the useful for studying the functions of these genes under specific pathological conditions.

Keyword

Estrogen; estrogen receptors; knockout mice

MeSH Terms

Adipogenesis
Animals
Animals, Genetically Modified
Cardiovascular System
Estrogen Receptor alpha
Estrogen Receptor beta
Estrogens
Female
Gene Expression Regulation
Humans
Male
Mice
Mice, Knockout
Mice, Transgenic
Ovariectomy
Phenotype
Receptors, Cytoplasmic and Nuclear
Receptors, Estrogen
Transcription Factors
Estrogen Receptor alpha
Estrogen Receptor beta
Estrogens
Receptors, Cytoplasmic and Nuclear
Receptors, Estrogen
Transcription Factors

Figure

• 

  Figure 1 Mechanisms of estrogen receptor signaling pathway. Estrogen (E2) is able to bind to estrogen receptors (ERs). The ERs then dimerize and translocate into the nucleus. These complexes bind to estrogen response elements (EREs). ERs contain five domains with distinct functions. The A/B domain contains transcriptional activation function 1 (AF1). The C domain has the DNA binding domain and the D domain is a hinge region. The E/F domain encodes the AF2 region.

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