The effect of budesonide and triamcinolone acetonide on hepatic microsomal testosterone metabolism in the rat.
The hepatic microsomal metabolism of testosterone was studied in male rats after treatment with either budesonide or triamcinolone acetonide for 13 weeks. The in vitro metabolism was determined using a testosterone concentration of 35 nM which is comparable to the levels found in plasma. It was shown that the total microsomal testosterone metabolism was decreased in budesonide-treated rats and increased in rats treated with triamcinolone acetonide. The testosterone metabolites produced were measured and thus it was revealed that budesonide treatment brought about its effect through a 50% decrease in the activity of steroid 5 alpha-reductase, but did not affect other reductive enzymes, or the oxidation of testosterone. Triamcinolone acetonide treatment decreased steroid 5 alpha-reductase activity by 95% and also decreased the activities of steroid 3 alpha- and 3 beta-reductases by more than 90%. In addition, treatment with triamcinolone acetonide caused a 50% increase in the oxidative metabolism of testosterone, which resulted in the observed increase in total testosterone metabolism. The presence of 0.1 microM budesonide in the microsomal incubations was without effect on testosterone metabolism. However, 0.1 microM triamcinolone acetonide inhibited testosterone oxidation by 65%, without affecting the reductive pathway of testosterone metabolism.
Edwards
R J
RJ
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, U.K.
Freeling
A B
AB
Watson
D
D
Davies
D S
DS
D000818:Animals; D019819:Budesonide; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D011282:Pregnenediones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000378:metabolism*; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D011282:Pregnenediones; D013739:Testosterone; D019819:Budesonide; D014222:Triamcinolone Acetonide