title: Beta-sitosterol and 17beta-estradiol alter gonadal steroidogenic acute regulatory protein (StAR) expression in goldfish, Carassius auratus.
abstract: Fish exposed to the phytosterol beta-sitosterol (beta-sit) have decreased circulating hormone and cholesterol concentrations, and decreased gonadal intra-mitochondrial cholesterol pools. The current study examined the potential for beta-sit to alter abundance of the key cholesterol transport protein, steroidogenic acute regulatory (StAR) protein, which delivers cholesterol to the first and rate-limiting steroidogenic enzyme P450 side chain cleavage (P450(scc)) inside the mitochondria. Plasma testosterone (T) and lipids (cholesterol, lipoproteins and triglycerides) were also measured. Goldfish were exposed to 200 microg/g beta-sit (97% pure or as a 72.6% pure phytosterol mixture) and 10 microg/g 17beta-estradiol (E(2); estrogenic control) by intra-peritoneal Silastic implants for 21-days or for five-months. Plasma T was significantly decreased in male fish exposed to the phytosterol mixture following the long-term exposure (p<0.001). There were no differences in total cholesterol concentrations among treatments in the short- or long-term exposure, but male fish in the long-term exposure had significantly lower HDL as compared to control fish (p<0.025) with a corresponding increase in LDL. StAR transcript levels were unchanged following the short-term exposure, but were reduced after five months in male beta-sit fish (p=0.05) and E(2)-treated female fish (p=0.05). This reduction in StAR transcript abundance in conjunction with decreased plasma T and altered plasma lipoprotein fractions demonstrates a non-estrogenic effect of beta-sit. This is the first study to show that beta-sit has the capacity to alter gonadal StAR transcript abundance, offering a mechanism by which beta-sit disrupts reproductive endocrine endpoints.
authors.affiliation: Canadian Rivers Institute and Department of Biology, University of New Brunswick (Saint John), PO Box 5050, Tucker Park Road, Saint John, NB, Canada E2L 4L5. rainie@ualberta.ca
authors.forename: Rainie L
authors.initials: RL
authors.lastname: Sharpe
authors.forename: Amanda
authors.initials: A
authors.lastname: Woodhouse
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Moon
authors.forename: Vance L
authors.initials: VL
authors.lastname: Trudeau
authors.forename: Deborah L
authors.initials: DL
authors.lastname: MacLatchy
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006054:Goldfish / Q000235:genetics / Q000378:metabolism*; D006066:Gonads / Q000187:drug effects / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D015394:Molecular Structure; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012855:Sitosterols / Q000737:chemistry / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood; D014158:Transcription, Genetic / Q000187:drug effects; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D008055:Lipids; D010750:Phosphoproteins; D012855:Sitosterols; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D004958:Estradiol; C025473:gamma-sitosterol; D002784:Cholesterol