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Int J Obes (Lond). 2012 Jul;36(7):982-5. doi: 10.1038/ijo.2011.172. Epub 2011 Aug 30.

Regulation of LKB1 expression by sex hormones in adipocytes.

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  • 1Endocrinology Unit, BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, UK.

Abstract

OBJECTIVE:

In the adipose tissue, activation of AMP-activated protein kinase (AMPK) by phosphorylation favours local fatty acid oxidation and inhibition of lipogenesis. We have previously shown that the potent androgen dihydrotestosterone (DHT) can inhibit phosphorylation of AMPK in adipose tissue and 3T3-L1 adipocytes in a dose-dependent manner. This negative effect of DHT was reversed by oestrogen treatment. The purpose of this current study was to determine the underlying mechanisms whereby androgens and oestrogens can regulate AMPK phosphorylation in adipocytes, and whether this mechanism is receptor dependent.

RESULTS:

Phosphorylation of AMPK was assessed by western blot in cells treated for 24 h with testosterone or DHT (1-1000 nM). Testosterone and DHT significantly inhibited basal phosphorylation of AMPK. Addition of the androgen receptor antagonist Flutamide (1 μM) to the media reversed the negative effect of testosterone and DHT by returning AMPK phosphorylation levels to those of basal. To further dissect the mechanism underlying AMPK inhibition by testosterone or DHT, we examined the mRNA expression of the upstream activator of AMPK, namely LKB1. Testosterone and DHT treatment of murine 3T3-L1 or human SGBS adipocytes for 24 h significantly decreased the mRNA expression of LKB1. In contrast, 17β-estradiol treatment increased LKB1 mRNA, an effect mediated by oestrogen receptor alpha.

CONCLUSION:

We conclude that regulation of AMPK phosphorylation by androgens and oestrogens is receptor-dependent, and demonstrate for the first time that LKB1 is regulated by sex hormones in adipocytes.

PMID:
21876548
[PubMed - indexed for MEDLINE]
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