Effects of some non-steroidal anti-inflammatory drugs (NSAIDS) on steroidogenesis in rat and porcine testis.
Using the rapid gas chromatographic steroid profiling technique, a number of metabolites of pregnenolone have been separated and quantified after incubation of this steroid with adult rat and neonatal porcine testicular homogenates. It was shown that the 5-ene-3 beta-hydroxy- and the 4-en-3-oxosteroid pathways for androgen biosynthesis were operating in both species, although the former pathway appeared to be more important in porcine testis. This tissue was characterised by the formation of several odorous, and pheromonal, 16-androstenes, which were quantitatively more important than the androgens. Three non-steroidal anti-inflammatory drugs (NSAIDS) caused dose-related inhibition of androgen and 16-androstene biosynthesis when co-incubated with pregnenolone. The order of potency was flurbiprofen > indomethacin > > > aspirin. The possibility that the NSAIDS may interfere with cytochrome P-450 is discussed, since several steroid-transforming enzymes, known to be dependent on this cytochrome for their activity, were markedly inhibited.
Kwan
T K
TK
Department of Biochemistry, Faculty of Medicine, University of Malaya, Kuala Lumpur.
Foong
S L
SL
Lim
Y T
YT
Gower
D B
DB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002849:Chromatography, Gas / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D011284:Pregnenolone / Q000378:metabolism*; D051381:Rats; D013552:Swine; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011284:Pregnenolone