Dehydroepiandrosterone metabolites and their interactions in humans.
Dehydroepiandrosterone (DHEA) is 7alpha-hydroxylated by the cytochrome P4507B1 in the liver, skin and brain, which are targets for glucocorticoids. 7alpha-Hydroxy-DHEA produced anti-glucocorticoid effects in vivo but the interference between the glucocorticoid hormone binding with its receptor could not be determined. In the organs mentioned above, circulating inactive cortisone is reduced to active cortisol by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). 7alpha-Hydroxy-DHEA is also a substrate for this enzyme. Studies of 11beta-HSD1 action on 7alpha-hydroxy-DHEA show the reversible production of 7beta-hydroxy-DHEA through an intermediary 7-oxo-DHEA. Both the production of 7alpha-hydroxysteroids and their interference with the activation of cortisone into cortisol are basic to the concept of native anti-glucocorticoids. The cytochrome P4507B1 responsible for 7alpha-hydroxy-DHEA production and 11beta-HSD1 are key enzymes for the modulation of glucocorticoid action in humans. This is a promising new area for research.
Chalbot
Sonia
S
Laboratoire de Biotechnologie, Conservatoire National des Arts et Métiers, Paris, France.
Morfin
Robert
R
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072474:Cytochrome P450 Family 7; D003687:Dehydroepiandrosterone / Q000737:chemistry / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008861:Microsomes; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013379:Substrate Specificity; D015003:Yeasts / Q000378:metabolism
D001647:Bile Acids and Salts; D003687:Dehydroepiandrosterone; D003577:Cytochrome P-450 Enzyme System; D042842:11-beta-Hydroxysteroid Dehydrogenases; D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human