-transparent.png){kind=logo}
Two 'neurosteroids', dehydroepiandrosterone (DHEA) and pregnenolone (PREG), are converted by rat brain microsomes into polar metabolites, identified as the respective 7 alpha-hydroxylated (7 alpha-OH) derivatives by the 'twin ion' technique of g.l.c.-m.s. with deuterated substrates. The enzymic reaction requires NADPH and is stimulated 2-4-fold by EDTA. Under optimal conditions (pH 7.4, 0.5 mM-NADPH, 1 mM-EDTA), the Km values for DHEA and PREG are 13.8 and 4.4 microM respectively, and the Vmax. values are 322 and 38.8 pmol/min per mg of microsomal protein respectively. Trace amounts of putative 7 beta-OH derivatives of DHEA and PREG are detected. Oestradiol, at a pharmacological concentration of 5 microM, inhibits DHEA and PREG 7 alpha-hydroxylation. Formation of 7 alpha-hydroxylated metabolites is low in prepubertal rats and increases 5-fold in adults. Derivatives of PREG and DHEA, such as PREG sulphate, DHEA sulphate, progesterone and 3 alpha-hydroxy-5 alpha-pregnan-20-one, are known to be neuroactive. Therefore the quantitatively important metabolism to 7 alpha-OH compounds may contribute to the control of neurosteroid activity in brain.
Y Akwa, and
R F Morfin, and
P Robel, and
E E Baulieu
January 1966,
Biochimica et biophysica acta,
Y Akwa, and
R F Morfin, and
P Robel, and
E E Baulieu
March 1995,
Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie,
Y Akwa, and
R F Morfin, and
P Robel, and
E E Baulieu
September 1972,
FEBS letters,
Y Akwa, and
R F Morfin, and
P Robel, and
E E Baulieu
May 1968,
Journal of lipid research,
Y Akwa, and
R F Morfin, and
P Robel, and
E E Baulieu
November 1998,
Steroids,
Y Akwa, and
R F Morfin, and
P Robel, and
E E Baulieu
June 2010,
Steroids,
Y Akwa, and
R F Morfin, and
P Robel, and
E E Baulieu
December 1963,
Experientia,
Y Akwa, and
R F Morfin, and
P Robel, and
E E Baulieu
October 1996,
Steroids,
Y Akwa, and
R F Morfin, and
P Robel, and
E E Baulieu
January 2001,
International review of neurobiology,
Y Akwa, and
R F Morfin, and
P Robel, and
E E Baulieu
January 1962,
Biochimica et biophysica acta,
