title: Possible association of heart failure status with synthetic balance between aldosterone and dehydroepiandrosterone in human heart.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Ito
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Eisaku
authors.initials: E
authors.lastname: Harada
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yasue
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: 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
chemical_list: 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