Email updates

Keep up to date with the latest news and content from Lipids in Health and Disease and BioMed Central.

Open Access Highly Accessed Research

Dihydrotestosterone regulating apolipoprotein M expression mediates via protein kinase C in HepG2 cells

Ye Yi-zhou1, Cao Bing2, Li Ming-qiu3, Wang Wei4, Wang Ru-xing3, Rui Jun3, Wei Liu-yan3, Jing Zhao-hui3, Ji Yong3, Jiao Guo qing3* and Zou Jian3*

Author Affiliations

1 Department of Cardiovascular Surgery, Affiliated Shanghai 1st People’s Hospital, Shanghai Jiaotong University, Shanghai, 210008, People's Republic of China

2 Department of Cardiothoracic Surgery, Affiliated Taixing People’s Hospital, Yangzhou Medical University, Taixing, 225400, People's Republic of China

3 Department of Cardiovascular Surgery, Affiliated Wuxi People’s Hospital, Nanjing Medical University, Qingyang Road 299, Wuxi City, Jiangsu Province, 214023, China

4 Department of Cardiovascular Surgery, National Center for Cardiovascular Disease, Beijing, 200000, People's Republic of China

For all author emails, please log on.

Lipids in Health and Disease 2012, 11:168  doi:10.1186/1476-511X-11-168

Published: 5 December 2012

Abstract

Background

Administration of androgens decreases plasma concentrations of high-density lipid cholesterol (HDL-C). However, the mechanisms by which androgens mediate lipid metabolism remain unknown. This present study used HepG2 cell cultures and ovariectomized C57BL/6 J mice to determine whether apolipoprotein M (ApoM), a constituent of HDL, was affected by dihydrotestosterone (DHT).

Methods

HepG2 cells were cultured in the presence of either DHT, agonist of protein kinase C (PKC), phorbol-12-myristate-13-acetate (PMA), blocker of androgen receptor flutamide together with different concentrations of DHT, or DHT together with staurosporine at different concentrations for 24 hrs. Ovariectomized C57BL/6 J mice were treated with DHT or vehicle for 7d or 14d and the levels of plasma ApoM and livers ApoM mRNA were measured. The mRNA levels of ApoM, ApoAI were determined by real-time RT-PCR. ApoM and ApoAI were determined by western blotting analysis.

Results

Addition of DHT to cell culture medium selectively down-regulated ApoM mRNA expression and ApoM secretion in a dose-dependent manner. At 10 nM DHT, the ApoM mRNA levels were about 20% lower than in untreated cells and about 40% lower at 1000 nM DHT than in the control cells. The secretion of ApoM into the medium was reduced to a similar extent. The inhibitory effect of DHT on ApoM secretion was not blocked by the classical androgen receptor blocker flutamide but by an antagonist of PKC, Staurosporine. Agonist of PKC, PMA, also reduced ApoM. At 0.5 μM PMA, the ApoM mRNA levels and the secretion of ApoM into the medium were about 30% lower than in the control cells. The mRNA expression levels and secretion of another HDL-associated apolipoprotein AI (ApoAI) were not affected by DHT. The levels of plasma ApoM and liver ApoM mRNA of DHT-treated C57BL/6 J mice were lower than those of vehicle-treated mice.

Conclusions

DHT directly and selectively down-regulated the level of ApoM mRNA and the secretion of ApoM by protein kinase C but independently of the classical androgen receptor.

Keywords:
Androgen; DHT; ApoM; PKC