Effects of ciprofibrate on testicular and adrenal steroidogenic enzymes in the rat.
Testicular and adrenal steroidogenic enzymes were measured radiometrically following oral dosing of rats with ciprofibrate (2-[4-(2,2-dichlorocyclopropyl) phenoxyl]-2-methylpropinoic acid), a peroxisome proliferator. Six-week-old male Fisher 344 rats were fed a diet containing ciprofibrate (0.025%, w/w) for 3, 7, 14, 28, 56, 84, 112 or 140 days leading to a daily ciprofibrate intake of approximately 15 mg/kg body weight/day. Ciprofibrate caused a marked inhibition of testicular 3beta-hydroxysteroid dehydrogenase-isomerase (3beta-HSD) activity that was significant after 3 days and subsequently decreased to 40% of control level. Ciprofibrate treatment also reduced 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity to a lesser extent but had no effect on 17-hydroxylase (17-OHase) activity. Immunoblot analyses indicated that ciprofibrate treatment did not alter enzyme protein levels and semi-quantitative RT-PCR analysis also revealed no significant changes in testicular 3beta-HSD mRNA levels. Furthermore, in addition to the enzyme-specific effect of ciprofibrate on 3beta-HSD in the testes, a tissue-specific effect was also evident, since no significant effects of ciprofibrate were seen on the activities of 3beta-HSD or 21-OHase in the adrenal glands from the same animals.
Hierlihy
Andrée M
AM
Toxicology Research Division, Food Directorate, Health Canada, Sir Frederick G. Banting Research Centre, 2202D1 Tunney's Pasture, Ottawa, Ont., Canada K1A 0L2.
Cooke
Gerard M
GM
Curran
Ivan H A
IH
Mehta
Rekha
R
Karamanos
Litsa
L
Price
Christopher A
CA
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000284:Administration, Oral; D000311:Adrenal Glands / Q000187:drug effects* / Q000201:enzymology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002995:Clofibric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D058607:Fibric Acids; D015870:Gene Expression / Q000187:drug effects; D015151:Immunoblotting; D007985:Leydig Cells / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000473:pathology; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D020025:Peroxisome Proliferators / Q000008:administration & dosage / Q000494:pharmacology; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013251:Steroid Isomerases / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D004798:Enzymes; D058607:Fibric Acids; D009097:Multienzyme Complexes; D020025:Peroxisome Proliferators; D012333:RNA, Messenger; D014280:Triglycerides; D002995:Clofibric Acid; D002784:Cholesterol; D015067:17-Hydroxysteroid Dehydrogenases; D011375:Progesterone Reductase; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D013251:Steroid Isomerases; C019304:ciprofibrate