Expression and Subcellular Localization of Estrogen Receptors α and β in Human Fetal Brown Adipose Tissue

Context: Brown adipose tissue (BAT) has the unique ability of generating heat due to the expression of mitochondrial uncoupling protein 1 (UCP1). A recent discovery regarding functional BAT in adult humans has increased interest in the molecular pathways of BAT development and functionality. An impo...

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Published in:The journal of clinical endocrinology and metabolism 2014-01, Vol.99 (1), p.151-159
Main Authors: Velickovic, Ksenija, Cvoro, Aleksandra, Srdic, Biljana, Stokic, Edita, Markelic, Milica, Golic, Igor, Otasevic, Vesna, Stancic, Ana, Jankovic, Aleksandra, Vucetic, Milica, Buzadzic, Biljana, Korac, Bato, Korac, Aleksandra
Format: Article
Language:English
Subjects:
Adipose Tissue, Brown - embryology
Adipose Tissue, Brown - growth & development
Adipose Tissue, Brown - metabolism
Biological and medical sciences
Endocrinopathies
Estrogen Receptor alpha - metabolism
Estrogen Receptor beta - metabolism
Feeding. Feeding behavior
Fetus - metabolism
Fundamental and applied biological sciences. Psychology
Gestational Age
Humans
Immunohistochemistry
Ion Channels - metabolism
Male
Medical sciences
Mitochondrial Proteins - metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
PPAR gamma - metabolism
Proliferating Cell Nuclear Antigen - metabolism
Tissue Distribution
Transcription Factors - metabolism
Uncoupling Protein 1
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Vertebrates: endocrinology
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Summary:Context: Brown adipose tissue (BAT) has the unique ability of generating heat due to the expression of mitochondrial uncoupling protein 1 (UCP1). A recent discovery regarding functional BAT in adult humans has increased interest in the molecular pathways of BAT development and functionality. An important role for estrogen in white adipose tissue was shown, but the possible role of estrogen in human fetal BAT (fBAT) is unclear. Objective: The objective of this study was to determine whether human fBAT expresses estrogen receptor α (ERα) and ERβ. In addition, we examined their localization as well as their correlation with crucial proteins involved in BAT differentiation, proliferation, mitochondriogenesis and thermogenesis including peroxisome proliferator-activated receptor γ (PPARγ), proliferating cell nuclear antigen (PCNA), PPARγ-coactivator-1α (PGC-1α), and UCP1. Design: The fBAT was obtained from 4 human male fetuses aged 15, 17, 20, and 23 weeks gestation. ERα and ERβ expression was assessed using Western blotting, immunohistochemistry, and immunocytochemistry. Possible correlations with PPARγ, PCNA, PGC-1α, and UCP1 were examined by double immunofluorescence. Results: Both ERα and ERβ were expressed in human fBAT, with ERα being dominant. Unlike ERβ, which was present only in mature brown adipocytes, we detected ERα in mature adipocytes, preadipocytes, mesenchymal and endothelial cells. In addition, double immunofluorescence supported the notion that differentiation in fBAT probably involves ERα. Immunocytochemical analysis revealed mitochondrial localization of both receptors. Conclusion: The expression of both ERα and ERβ in human fBAT suggests a role for estrogen in its development, primarily via ERα. In addition, our results indicate that fBAT mitochondria could be targeted by estrogens and pointed out the possible role of both ERs in mitochondriogenesis.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2013-2017