| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Center of Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Aerosol Research, Hannover, Germany
1Correspondence: Fraunhofer Institute of Toxicology and Aerosol Research, Center for Drug Research and Medical Biotechnology, Nicolai-Fuchs-Str. 1, D-30659 Hannover, Germany. E-mail: Borlak{at}ita.fhg.de
Cytochrome P450 mono-oxygenases (CYP) play an essential role in steroid metabolism, and there is speculation that sex hormones might influence cardiac mass and physiology. As CYP mono-oxygenases activity is frequently altered during disease, we tested our hypothesis that CYP mono-oxygenase expression and testosterone metabolism are altered in cardiac hypertrophy. We investigate major CYP mono-oxygenase isoforms and other steroid-metabolizing enzymes and the androgen receptor in normal, hypertrophic, and assist device-supported human hearts and in spontaneously hypertensive rats (SHR). We show increased and idiosyncratic metabolism of testosterone in hypertrophic heart and link these changes to altered CYP mono-oxygenase expression. We show significant induction of 5-alpha steroid reductase and P450 aromatase gene expression and enhanced production of dihydrotestosterone, which can be inhibited by the 5-alpha reductase inhibitor finasteride. We show increased gene expression of the androgen receptor and increased levels of lipid peroxidation in diseased hearts, the latter being markedly inhibited by CYP mono-oxygenase inactivation. We show alpha-MHC to be significantly repressed in cardiac hypertrophy and restored to normal on testosterone supplementation. We conclude that heart-specific steroid metabolism is of critical importance in cardiac hypertrophy.—Thum, T., Borlak, J. Testosterone, cytochrome P450, and cardiac hypertrophy.
Key Words: CYP • cytochrome P450 mono-oxygenases • testosterone metabolism • cardiac hypertrophy
This article has been cited by other articles:
|
|
 |
|
  J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Tivesten, E Bollano, H C Nystrom, C Alexanderson, G Bergstrom, and A Holmang Cardiac concentric remodelling induced by non-aromatizable (dihydro-)testosterone is antagonized by oestradiol in ovariectomized rats. J. Endocrinol., June 1, 2006; 189(3): 485 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Gao, P. J. Reiser, C. C. Coss, M. A. Phelps, J. D. Kearbey, D. D. Miller, and J. T. Dalton Selective Androgen Receptor Modulator Treatment Improves Muscle Strength and Body Composition and Prevents Bone Loss in Orchidectomized Rats Endocrinology, November 1, 2005; 146(11): 4887 - 4897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Borlak, I. Schulte, and T. Thum ANDROGEN METABOLISM IN THYMUS OF FETAL AND ADULT RATS Drug Metab. Dispos., June 1, 2004; 32(6): 675 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Thum and J. Borlak Mechanistic Role of Cytochrome P450 Monooxygenases in Oxidized Low-Density Lipoprotein-Induced Vascular Injury: Therapy Through LOX-1 Receptor Antagonism? Circ. Res., January 9, 2004; 94 (1): e1 - e13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. BORLAK and T. THUM Hallmarks of ion channel gene expression in end-stage heart failure FASEB J, September 1, 2003; 17(12): 1592 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Y. Liu, A. K. Death, and D. J. Handelsman Androgens and Cardiovascular Disease Endocr. Rev., June 1, 2003; 24(3): 313 - 340. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
