Receptor binding and biological activity of 18-oxocortisol.
It has been recently demonstrated that cortisol can be metabolized, producing 18-hydroxycortisol and 18-oxocortisol, following the same pathway by which corticosterone is transformed into 18-hydroxycorticosterone and aldosterone. The influence of a hydroxy group in the 17 alpha position of aldosterone or an aldehyde (actually 11-18 hemiacetal) in the 13-methyl of cortisol on the mineralocorticoid and glucocorticoid activities were studied and compared with the parent steroids. The ability of 18-oxocortisol to complete with [3H]aldosterone for binding to the cytosol receptor of rat renal slices was 8.1% in comparison to unlabeled aldosterone. The addition of a specific glucocorticoid 11 beta, 17 beta-dihydroxy-17 alpha-pregnane-1,4,6- trien-20-yn-21-methyl-3-one decreased this binding to 5.6%. The ability of 18-oxocortisol to compete with [3H]dexamethasone for binding to the renal cytosol receptor was 0.2% that of unlabeled dexamethasone and in the HTC whole cell assay was 1.06% and 3.8% that of unlabeled dexamethasone and cortisol, respectively. The mineralocorticoid activity of 18-oxocortisol in the adrenalectomized rat bioassay was 0.6% that of aldosterone. The glucocorticoid activity in in vitro bioassays was 3.1% compared with that of a cortisol when the induction of tyrosine aminotransferase in HTC cells was measured and 4% when the inhibition of fibroblast L-929 growth was measured. The significance of 18-oxocortisol in the pathogenesis of the hypertension in patients with primary aldosteronism is still unclear.
Gomez-Sanchez
C E
CE
Gomez-Sanchez
E P
EP
Smith
J S
JS
Ferris
M W
MW
Foecking
M F
MF
D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001681:Biological Assay; D003600:Cytosol / Q000378:metabolism*; D003907:Dexamethasone / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014444:Tyrosine Transaminase / Q000096:biosynthesis
D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; C038135:18-oxocortisol; D000450:Aldosterone; D003907:Dexamethasone; D012964:Sodium; D014444:Tyrosine Transaminase; D011188:Potassium; D006854:Hydrocortisone