Interactions of retinoic acid and androgens in human prostatic tissue.
The effect of retinoic acid (RA) on testosterone metabolic pathway was investigated in hyperplastic and neoplastic human prostatic tissues, and also the effects of steroids on RA binding to its receptor. Steroids only had a minimal effect on the binding of RA by its receptor. The conversion of testosterone to DHT by 5 alpha-reductase was reduced in the presence of retinoic acid. The inhibition was probably due to competition with NADPH for enzyme binding sites. The degree of inhibition found with retinoic acid at a concentration of 10(-4)M was greater for hyperplastic (41%) than that for neoplastic tissue (24%). The inhibition of 5 alpha-reductase by retinoic acid was dose-dependent. The activity of 5 alpha-reductase is significantly less in neoplastic compared with hyperplastic tissue.
Jutley
J K
JK
Department of Medicine, St. James's University Hospital, Leeds, England.
Reaney
S
S
Kelleher
J
J
Whelan
P
P
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000032:analysis; D058891:5-alpha Reductase Inhibitors; D002352:Carrier Proteins / Q000032:analysis; D006801:Humans; D008297:Male; D009249:NADP / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000201:enzymology*; D011470:Prostatic Hyperplasia / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology; D018168:Receptors, Retinoic Acid; D014212:Tretinoin / Q000494:pharmacology*
D058891:5-alpha Reductase Inhibitors; D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D009249:NADP; D014212:Tretinoin; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase