Specificity and structural relationships of steroids which affect phospholipase/prostaglandin synthetase, in vivo: a possible relation to blood pressure.
Fifty-two steroids, structurally related to spironolactone, were tested for their ability to alter excretion of urinary prostaglandin-E metabolites (U-PGE-M). We found that steroids which are associated with elevation or depression of blood pressure will elevate or depress basal levels of U-PGE-M in the rat. Structural requirements for elevation or depression of metabolites are narrow and sensitive to slight conformational changes in either the C-17 side chain or the steroid nucleus. Metabolite-elevating steroids share a common basic conformation, and metabolite-depressing steroids share a different common basic conformation. These two basic conformations differ chiefly in the C-17 side chain. The conformational requirements are analogous to the specificity shown by hormone receptors or by enzymes. A strong association of urine volume with U-PGE-M (r = -0.93) was demonstrated in rats treated with spironolactone. A possible explanation relating these results to alteration of blood pressure was presented.
D000818:Animals; D001794:Blood Pressure; D008297:Male; D010740:Phospholipases / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011458:Prostaglandins E / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011458:Prostaglandins E; D013148:Spironolactone; D011451:Prostaglandin-Endoperoxide Synthases; D010740:Phospholipases