7-Hydroxydehydroepiandrosterone--a natural antiglucocorticoid and a candidate for steroid replacement therapy?
7-Hydroxylated metabolites of dehydroepiandrosterone (DHEA) are believed to be responsible for at least some immunomodulatory and antiglucocorticoid effects of DHEA and hence are considered candidates for hormone replacement therapy. Our experiments in vitro brought the evidence that 3beta, 7beta-dihydroxy-5-androsten-3-one (7beta-OH-DHEA), but not DHEA and its 7alpha-hydroxyisomer, could counteract the immunosuppressive effect of dexamethasone on the formation of plaques in culture of murine spleen lymphocytes. In another experiment, DHEA and after a 3-weeks pause 3beta-hydroxy-5-androstene-7,17-dione (7-oxo-DHEA) were applied transdermally to 6 male volunteers on 5 consecutive days. Blood levels of DHEA, its 7-hydroxylated metabolites, and in the first case also dehydroepiandrosterone sulphate (DHEAS), were measured before, during and one day after the end of treatment. Application of DHEA increased significantly not only DHEA and DHEAS, but also its both 7-hydroxyisomers. Application of 7-oxo-DHEA also led to a significant increase of both 7-hydroxyisomers of DHEA, with 7beta-OH-DHEA being the preferred metabolite the concentration of which was increased more than three times.
Hampl
R
R
Institute of Endocrinology, Czech Academy of Sciences, Prague, Czech Republic. rhampl@endo.cz
Lapcík
O
O
Hill
M
M
Klak
J
J
Kasal
A
A
Novácek
A
A
Sterzl
I
I
Sterzl
J
J
Stárka
L
L
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007536:Isomerism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D010865:Pilot Projects; D010948:Viral Plaque Assay
D005938:Glucocorticoids; D003687:Dehydroepiandrosterone; C003587:7-hydroxydehydroepiandrosterone; D003907:Dexamethasone; C117281:3-acetoxyandrost-5-ene-7,17-dione