Rat liver 3 alpha-hydroxysteroid dehydrogenase.
3 alpha-HSD appears to be a multifunctional enzyme. In addition to its traditional role of catalyzing early steps in androgen metabolism, it will also oxidoreduce prostaglandins and detoxify trans-dihydrodiols (proximate carcinogens). Since these novel reactions have been quantified using homogeneous enzyme it is necessary to interpret the role of the enzyme in these processes in vivo with some caution. However, it is rare that such observations on a purified hydroxysteroid dehydrogenase have led to such important questions. Is the 3 alpha-HSD the only steroid dehydrogenase that transforms prostaglandins and trans-dihydrodiols? Are hydroxysteroid dehydrogenases and prostaglandin dehydrogenases the same enzymes in certain tissues? Does 3 alpha-HSD protect against chemical carcinogenesis in vivo? The inhibition of the purified dehydrogenase by therapeutically relevant concentrations of anti-inflammatory drugs also deserves comment. Is this hydroxysteroid dehydrogenase really an in vivo target for anti-inflammatory drug action? Could these drugs exert some of their pharmacological effect either by preventing glucocorticoid metabolism in some tissues or by preventing the transformation of PGF2 alpha (non-inflammatory prostanoid) to PGE2 (a pro-inflammatory prostanoid)? Could these drugs, by inhibiting trans-dihydrodiol oxidation, potentiate the initiation of chemical carcinogenesis? These and other important questions can be answered only by developing specific inhibitors for the dehydrogenase to decipher its function in vivo.
Penning
T M
TM
Smithgall
T E
TE
Askonas
L J
LJ
Sharp
R B
RB
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008099:Liver / Q000201:enzymology*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D002273:Carcinogens; D011453:Prostaglandins; D011955:Receptors, Drug; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)