title: An investigation of the effects of methylmercury in rats fed different dietary fats and proteins: testicular steroidogenic enzymes and serum testosterone levels.
abstract: Methylmercury (MeHg) is a testicular toxicant causing reduced steroidogenic enzyme activity, reduced serum testosterone (T) and abnormal spermatogenesis in mammals and fowl. It is also known that certain diets can alter androgen metabolism in rats. Previously we have shown that diets used in the current study impact circulating androgen levels and testicular steroidogenic enzyme activities in Sprague Dawley rats in the absence of MeHg. In the present study, we have investigated the impact of imposing an environmental contaminant (MeHg) commonly found in marine mammals and fish onto the rats' dietary intake of different proteins and lipids in order to determine if the different diets could modify MeHg toxicity in rats. Therefore, we examined the effects of MeHg on testicular steroidogenic enzymes and serum testosterone in rats fed diets containing either different protein sources (casein, fishmeal, whey) or different lipid sources (soybean oil, docosahexaenoic acid (DHA), seal oil, fish oil, lard). Male rats 42-45 days of age (18 per group) were assigned to different experimental diets for 28 days after which 6 rats in each group were gavaged daily with 0, 1 or 3 mg/kg body weight (BW)/day MeHg chloride in 5 mM Na(2)CO(3) solution for 14 days while being maintained on their diets. On the 43rd day of dosing, rats were sacrificed and blood plasma and testes frozen (-80 degrees C) until analysis. Microsomal steroidogenic enzyme activities (3beta-HSD, 17-OHase, C-17, 20-lyase, 17beta-HSD) were measured radiometrically. Serum testosterone was determined using ELISA kits. Testis weights were not affected by MeHg. MeHg at 3 mg/kg BW/day caused a reduction (>50%) in the activity of C-17, 20-lyase in all three protein diets and similar reductions in 17-OHase activity were seen in the casein and whey protein fed rats. At 3 mg/kg BW/day, MeHg reduced 17-OHase activity in the DHA diet but had no effect on 3beta-HSD activity and no inhibitory effects on 17beta-HSD activity. MeHg (3 mg/kg BW/day) caused significant reductions in serum T in the whey, soybean oil and fish oil groups. Interestingly, fishmeal protein but not fish oil offered some protection with respect to maintaining steroidogenic enzyme activities and serum T levels in rats dosed with MeHg. In conclusion, these studies show that different lipid diets can alter the toxic effects of MeHg on male rat steroidogenesis in terms of serum testosterone and steroidogenic enzyme activities.
authors.affiliation: Toxicology Research Division, Health Products and Foods Branch, Food Directorate, Health Canada, Sir Fredrick G. Banting Research Centre, 2202D1 Tunney's Pasture, Ottawa, ON, Canada K1A 0L2.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: McVey
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Cooke
authors.forename: Ivan H A
authors.initials: IH
authors.lastname: Curran
authors.forename: Hing Man
authors.initials: HM
authors.lastname: Chan
authors.forename: Stan
authors.initials: S
authors.lastname: Kubow
authors.forename: Eric
authors.initials: E
authors.lastname: Lok
authors.forename: Rekha
authors.initials: R
authors.lastname: Mehta
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000728:Androgens / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D004044:Dietary Proteins / Q000494:pharmacology*; D006801:Humans; D004930:Inuit; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013737:Testis / Q000187:drug effects / Q000201:enzymology*; D013739:Testosterone / Q000097:blood*
chemical_list: D000728:Androgens; D004041:Dietary Fats; D004044:Dietary Proteins; D008767:Methylmercury Compounds; D013256:Steroids; D013739:Testosterone; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase