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This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/E340    most recent 00175.2006v2 00175.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Rodríguez-Cuenca, S. Articles by Roca, P. Search for Related Content PubMed PubMed Citation Articles by Rodríguez-Cuenca, S. Articles by Roca, P.

Expression of mitochondrial biogenesis-signaling factors in brown adipocytes is influenced specifically by 17-estradiol, testosterone, and progesterone

¹Grup de Metabolisme Energètic i Nutrició, Departament de Biologia Fonamental i Ciències de la Salut, Institut Universitari d'Investigació en Ciències de la Salut, Universitat de les Illes Balears, Palma de Mallorca, Spain; and ²Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, Oslo, Norway

Submitted 12 April 2006 ; accepted in final form 28 August 2006

Control of mitochondrial biogenesis in brown adipose tissue (BAT), as part of the thermogenesis program, is a complex process that requires the integration of multiple transcription factors to orchestrate mitochondrial and nuclear gene expression. Despite the knowledge of the role of sex hormones on BAT physiology, little is known about the effect of these hormones on the mitochondrial biogenic program. The aim of this study was to determine the effect of testosterone, 17-estradiol, and progesterone on the expression of nuclear factors involved in the control of mitochondrial biogenesis and thermogenic function such as ppar, pgc1, nrf1, gabpa, and tfam, and also an inhibitor of PI3K-Akt pathway, recently found to be involved in the control of mitochondrial recruitment (pten). For this purpose, an in vitro assay using cell-cultured brown adipocytes was used to address the role of steroid hormones, progesterone, testosterone, and 17-estradiol on the mRNA expression of these factors by real-time PCR. Thus 17-estradiol seemed to exert a dual effect, activating the PI3K-Akt pathway by inhibiting pten mRNA expression and also inhibiting nrf1 and tfam mRNA expression. Progesterone seemed to positively stimulate mitochondriogenesis and BAT differentiation by increasing the mRNA expression of the gabpa-tfam axis and ppar, respectively, but also exerted a negative output by increasing pten mRNA levels. Finally, testosterone inhibited the transcription of pgc1, the master factor involved in UCP1 expression and mitochondrial biogenesis. In conclusion, our results support the idea that sex hormones have direct effects on different mediators of the mitochondriogenesis program.

brown adipose tissue; sex steroids; mitochondriogenesis program signaling; nuclear and mitochondrial transcription factors

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