PMID- 18261897
OWN - NLM
STAT- MEDLINE
DCOM- 20080603
LR  - 20161124
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 109
IP  - 1-2
DP  - 2008 Mar
TI  - DHEA decreases HIF-1alpha accumulation under hypoxia in human pulmonary artery 
      cells: potential role in the treatment of pulmonary arterial hypertension.
PG  - 81-9
LID - 10.1016/j.jsbmb.2007.12.001 [doi]
AB  - Previous work showed that dehydroepiandrosterone (DHEA) prevents and reverses 
      chronic hypoxic pulmonary artery hypertension in rat via targeting smooth muscle 
      cells. In our study, DHEA was tested on human pulmonary arterial smooth muscle 
      cells (HPASMC) to identify its mechanism of action under hypoxia in vitro. We 
      show that DHEA decreased HIF-1alpha accumulation under both "chemical hypoxia" 
      with treatment by the iron chelator deferroxamin and gas hypoxia (1% O2). The 
      mRNA levels of HIF-1alpha were unchanged whether or not DHEA was applied under 
      chemical and gas hypoxia, as compared to controls in normoxia, suggesting a 
      post-transcriptional effect of the steroid. Protein levels of prolyl hydroxylases 
      responsible for HIF-1alpha degradation were not modified by DHEA treatment. In 
      addition, a synthetic derivative of DHEA, 3beta-methyl-Delta5-androsten-17-one 
      (which cannot be metabolized), was as active as DHEA on HIF-1alpha accumulation, 
      as well as testosterone and 17beta-estradiol (E2). In HPASMC cultures under 
      normoxia and both types of hypoxia, DHEA gave rise to 
      Delta5-androstene-3beta,17beta-diol (ADIOL) and DHEA-sulfate (DHEA-S). Neither 
      testosterone, nor E2 were found. In addition, ADIOL, DHEA-S, 7alpha-hydroxy-DHEA 
      and Delta4-androstene-3,17-dione were ineffective on HIF-1alpha accumulation. The 
      effect of DHEA per se reducing HIF-1alpha accumulation may be relevant to reduced 
      hypoxia effects in pulmonary arterial hypertension.
FAU - Dessouroux, A
AU  - Dessouroux A
AD  - INSERM U788 and Universite Paris-Sud, Faculte de medecine, UMR-S788, 80 rue du 
      General Leclerc, F-94276, le Kremlin Bicetre, France.
FAU - Akwa, Y
AU  - Akwa Y
FAU - Baulieu, E E
AU  - Baulieu EE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071207
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Amino Acids, Dicarboxylic)
RN  - 0 (DNA Primers)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Iron Chelating Agents)
RN  - 3G0H8C9362 (Cobalt)
RN  - 3XMK78S47O (Testosterone)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
RN  - EVS87XF13W (cobaltous chloride)
RN  - J06Y7MXW4D (Deferoxamine)
RN  - VVW38EB8YS (oxalylglycine)
SB  - IM
MH  - Amino Acids, Dicarboxylic/pharmacology
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Cobalt/pharmacology
MH  - DNA Primers/genetics
MH  - Deferoxamine/pharmacology
MH  - Dehydroepiandrosterone/analogs & derivatives/metabolism/*pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Estradiol/pharmacology
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy/etiology/genetics/*metabolism
MH  - Hypoxia/complications/*drug therapy/genetics/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Iron Chelating Agents/pharmacology
MH  - Models, Cardiovascular
MH  - Myocytes, Smooth Muscle/drug effects/metabolism
MH  - Procollagen-Proline Dioxygenase/antagonists & inhibitors/metabolism
MH  - Pulmonary Artery/cytology/*drug effects/*metabolism
MH  - Testosterone/pharmacology
EDAT- 2008/02/12 09:00
MHDA- 2008/06/05 09:00
CRDT- 2008/02/12 09:00
PHST- 2008/02/12 09:00 [pubmed]
PHST- 2008/06/05 09:00 [medline]
PHST- 2008/02/12 09:00 [entrez]
AID - S0960-0760(07)00273-7 [pii]
AID - 10.1016/j.jsbmb.2007.12.001 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2008 Mar;109(1-2):81-9. doi: 
      10.1016/j.jsbmb.2007.12.001. Epub 2007 Dec 7.