Transformations of DHEA and its metabolites by rat liver.
Because dehydroepiandrosterone (DHEA) has a wide variety of weak beneficial effects in experimental animals and humans, we searched for metabolites of this steroid in the hope of finding more active compounds that might qualify for the title "steroid hormone." Incubation of DHEA with rat liver homogenate fortified with energy-yielding substrates resulted in rapid hydroxylation at the 7alpha-position of the molecule and subsequent conversion to other 7-oxygenated steroids in the sequence DHEA --> 7alpha-hydroxyDHEA --> 7-oxoDHEA --> 7beta-hydroxyDHEA, with branching to diols, triols, and sulfate esters. The ability of these metabolites to induce the formation of liver thermogenic enzyme activity increased from left to right in that sequence. A total of 25 different steroids were characterized, and at least six additional structures that are currently under study were produced from DHEA. 7-OxoDHEA is more effective than DHEA in enhancing memory performance in old mice and in reversing the amnesic effects of scopolamine.
Lardy
Henry
H
Department of Biochemistry and Institute for Enzyme Research, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. halardy@facstaff.wisc.edu
Marwah
Ashok
A
Marwah
Padma
P
D000818:Animals; D001711:Biotransformation; D003687:Dehydroepiandrosterone / Q000737:chemistry / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats
D003687:Dehydroepiandrosterone