Functional potentiation of leptin-signal transducer and activator of transcription 3 signaling by the androgen receptor

Wu Qiang Fan, Toshihiko Yanase, Yoshihiro Nishi, Seiichi Chiba, Taijiro Okabe, Masatoshi Nomura, Hironobu Yoshimatsu, Shigeaki Kato, Ryoichi Takayanagi, Hajime Nawata

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Hypogonadism is associated with increased fat mass and dysregulation of metabolic homeostasis in men. Our previous study revealed that androgen receptor (AR)-null male mice (ARL-/Y) develop late-onset obesity and are leptin-resistant. The present study evaluated how hypothalamic AR contributes to central leptin-signal transducer and activator of transcription 3 (STAT3) signaling. We evaluated leptin action in wild-type and ARL-/Y mice, the anatomic co-relationship between AR and leptin signaling in the hypothalamus, and the effects of AR on leptin-mediated STAT3 transactivation and nuclear translocation. AR deletion in male mice results in a weaker leptin-induced suppression of food intake and body weight drop even before the onset of overt obesity. In wild-type male but not female mice, AR was highly expressed in various hypothalamic nuclei that also expressed the long-form leptin receptor (OBRB) and co-resided with OBRB directly in the arcuate neurons. In vitro, AR significantly enhanced STAT3-mediated transcription of leptin target genes including POMC and SOCS3. This effect relied on the AR N-terminal activation function-1 (AF-1) domain and was specific to AR in that none of the other sex steroid hormone receptors tested showed similar effects. AR enhanced the low concentrations of leptin-induced STAT3 nuclear translocation in vitro, and ARL-/Y mice receiving leptin had impaired STAT3 nuclear localization in the arcuate neurons. These findings indicate that AR in the hypothalamus functions as a regulator of central leptin-OBRB-STAT3 signaling and has a physiological role in energy homeostasis and metabolic regulation in male mice.

Original languageEnglish
Pages (from-to)6028-6036
Number of pages9
JournalEndocrinology
Volume149
Issue number12
DOIs
Publication statusPublished - Dec 1 2008

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STAT3 Transcription Factor
Androgen Receptors
Leptin
Hypothalamus
Homeostasis
Obesity
Neurons
Leptin Receptors
Pro-Opiomelanocortin
Hypogonadism
Steroid Receptors
Gonadal Steroid Hormones
Transcriptional Activation
Eating
Fats
Body Weight

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Fan, W. Q., Yanase, T., Nishi, Y., Chiba, S., Okabe, T., Nomura, M., ... Nawata, H. (2008). Functional potentiation of leptin-signal transducer and activator of transcription 3 signaling by the androgen receptor. Endocrinology, 149(12), 6028-6036. https://doi.org/10.1210/en.2008-0431

Functional potentiation of leptin-signal transducer and activator of transcription 3 signaling by the androgen receptor. / Fan, Wu Qiang; Yanase, Toshihiko; Nishi, Yoshihiro; Chiba, Seiichi; Okabe, Taijiro; Nomura, Masatoshi; Yoshimatsu, Hironobu; Kato, Shigeaki; Takayanagi, Ryoichi; Nawata, Hajime.

In: Endocrinology, Vol. 149, No. 12, 01.12.2008, p. 6028-6036.

Research output: Contribution to journalArticle

Fan, WQ, Yanase, T, Nishi, Y, Chiba, S, Okabe, T, Nomura, M, Yoshimatsu, H, Kato, S, Takayanagi, R & Nawata, H 2008, 'Functional potentiation of leptin-signal transducer and activator of transcription 3 signaling by the androgen receptor', Endocrinology, vol. 149, no. 12, pp. 6028-6036. https://doi.org/10.1210/en.2008-0431
Fan, Wu Qiang ; Yanase, Toshihiko ; Nishi, Yoshihiro ; Chiba, Seiichi ; Okabe, Taijiro ; Nomura, Masatoshi ; Yoshimatsu, Hironobu ; Kato, Shigeaki ; Takayanagi, Ryoichi ; Nawata, Hajime. / Functional potentiation of leptin-signal transducer and activator of transcription 3 signaling by the androgen receptor. In: Endocrinology. 2008 ; Vol. 149, No. 12. pp. 6028-6036.
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