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Am J Physiol Endocrinol Metab 288: E1222-E1228, 2005. First published January 18, 2005; doi:10.1152/ajpendo.00370.2004
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Marked attenuation of production of collagen type I from cardiac fibroblasts by dehydroepiandrosterone

Tomoyuki Iwasaki,1,* Koji Mukasa,1,* Masato Yoneda,1 Satoshi Ito,1 Yoshihiko Yamada,1 Yasumichi Mori,1 Nobutaka Fujisawa,1 Toshio Fujisawa,1 Koichiro Wada,2 Hisahiko Sekihara,1 and Atsushi Nakajima1

1Division of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama; and 2Department of Pharmacology, Graduate school of Dentistry, Osaka University, Osaka, Japan

Submitted 12 August 2004 ; accepted in final form 13 January 2005

Dehydroepiandrosterone (DHEA) is a type of adrenal steroid. The concentrations of DHEA and its sulfate (DHEA-S) in serum reach a peak between the ages of 25 and 30 yr and thereafter decline steadily. It was reported that DHEA-S concentration in humans is inversely related to death from cardiovascular diseases. In this study, we examined the effects of DHEA on regulation of collagen mRNA and collagen synthesis in cultured cardiac fibroblasts. Treatment with DHEA (10–6 M) resulted in a significant decrease in procollagen type I mRNA expression compared with controls. This was accompanied by a significant decrease in procollagen type I protein accumulation in the medium and also a significant decrease in procollagen type I protein synthesis in the cellular matrix. Furthermore, to confirm in vitro results, we administered DHEA to Sprague-Dawley rats, which were treated with angiotensin II for 8 wk to induce cardiac damage. Procollagen type I mRNA expression was significantly decreased and cardiac fibrosis significantly inhibited in DHEA-treated rat hearts without lowering the systolic blood pressure. These results strongly indicate that DHEA can directly attenuate collagen type I synthesis at the transcriptional level in vivo and in vitro in cardiac fibroblasts.

collagen type III; heart; procollagen type I


Address for reprint requests and other correspondence: A. Nakajima, Division of Endocrinology and Metabolism, Yokohama City Univ. Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan (E-mail: nakajima-tky{at}umin.ac.jp)




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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. M. Alwardt, Q. Yu, H. L. Brooks, M. R. McReynolds, R. Vazquez, R. R. Watson, and D. F. Larson
Comparative effects of dehydroepiandrosterone sulfate on ventricular diastolic function with young and aged female mice
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R251 - R256.
[Abstract] [Full Text] [PDF]


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