Possible association of heart failure status with synthetic balance between aldosterone and dehydroepiandrosterone in human heart.
BACKGROUND
Aldosterone is produced not only in the adrenal gland but also in the extra-adrenal tissues, including failing human heart. This study examined the production of dehydroepiandrosterone (DHEA) in human heart and elucidated the possible physiological significance. Method and Results- Using left ventricular tissues obtained at autopsy, reverse transcription-polymerase chain reaction followed by Southern blot analysis revealed the gene expressions of CYP17. By measuring plasma aldosterone and DHEA levels at the coronary sinuses and aortic roots during cardiac catheterization, we found that DHEA but not aldosterone was secreted from control subjects (P<0.0001 and P=0.74, respectively), whereas aldosterone but not DHEA was secreted from patients with heart failure (P=0.0017 and P=0.67, respectively). To examine the significance of DHEA, we measured myocyte cell sizes and the gene expression of B-type natriuretic peptide (BNP), using a neonatal rat cardiocyte culture system. We found that DHEA (10(-8) mol/L) significantly inhibited the increase in myocyte cell sizes and BNP mRNA levels upregulated by endothelin-1 (P=0.031 and P<0.0001, respectively).


CONCLUSIONS
CYP17 gene expression and production of DHEA were demonstrated in human control heart. Also, we found that cardiac production of DHEA was suppressed in failing heart. We postulated that DHEA and/or its metabolites exert a cardioprotective action through antihypertrophic effects.
Nakamura
Shota
S
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto, Japan.
Yoshimura
Michihiro
M
Nakayama
Masafumi
M
Ito
Teruhiko
T
Mizuno
Yuji
Y
Harada
Eisaku
E
Sakamoto
Tomohiro
T
Saito
Yoshihiko
Y
Nakao
Kazuwa
K
Yasue
Hirofumi
H
Ogawa
Hisao
H
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D015139:Blotting, Southern; D006328:Cardiac Catheterization; D048429:Cell Size; D002478:Cells, Cultured / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006352:Heart Ventricles / Q000201:enzymology; D006801:Humans; D006984:Hypertrophy; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013252:Steroid 11-beta-Hydroxylase / Q000096:biosynthesis / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics
D019332:Endothelin-1; D012333:RNA, Messenger; C495963:natriuretic peptide precursor type B, rat; D020097:Natriuretic Peptide, Brain; D003687:Dehydroepiandrosterone; D000450:Aldosterone; D013254:Steroid 17-alpha-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase