Abstract
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.
MeSH terms
-
17-Hydroxysteroid Dehydrogenases / genetics
-
17-Hydroxysteroid Dehydrogenases / metabolism
-
Administration, Oral
-
Adrenal Glands / drug effects*
-
Adrenal Glands / enzymology
-
Animals
-
Body Weight / drug effects
-
Cholesterol / blood
-
Clofibric Acid / administration & dosage
-
Clofibric Acid / analogs & derivatives*
-
Clofibric Acid / pharmacology
-
Dose-Response Relationship, Drug
-
Enzymes / genetics
-
Enzymes / metabolism*
-
Fibric Acids
-
Gene Expression / drug effects
-
Immunoblotting
-
Leydig Cells / drug effects*
-
Leydig Cells / enzymology
-
Liver / pathology
-
Male
-
Multienzyme Complexes / genetics
-
Multienzyme Complexes / metabolism
-
Organ Size / drug effects
-
Peroxisome Proliferators / administration & dosage
-
Peroxisome Proliferators / pharmacology
-
Progesterone Reductase / genetics
-
Progesterone Reductase / metabolism
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Rats
-
Rats, Inbred F344
-
Reverse Transcriptase Polymerase Chain Reaction
-
Steroid 17-alpha-Hydroxylase / genetics
-
Steroid 17-alpha-Hydroxylase / metabolism
-
Steroid 21-Hydroxylase / genetics
-
Steroid 21-Hydroxylase / metabolism
-
Steroid Isomerases / genetics
-
Steroid Isomerases / metabolism
-
Triglycerides / blood
Substances
-
3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase
-
Enzymes
-
Fibric Acids
-
Multienzyme Complexes
-
Peroxisome Proliferators
-
RNA, Messenger
-
Triglycerides
-
Clofibric Acid
-
Cholesterol
-
17-Hydroxysteroid Dehydrogenases
-
Progesterone Reductase
-
Steroid 21-Hydroxylase
-
Steroid 17-alpha-Hydroxylase
-
Steroid Isomerases
-
ciprofibrate