β-Sitosterol and 17β-estradiol alter gonadal steroidogenic acute regulatory protein (StAR) expression in goldfish, Carassius auratus

Fish exposed to the phytosterol β-sitosterol (β-sit) have decreased circulating hormone and cholesterol concentrations, and decreased gonadal intra-mitochondrial cholesterol pools. The current study examined the potential for β-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 (P450scc) inside the mitochondria. Plasma testosterone (T) and lipids (cholesterol, lipoproteins and triglycerides) were also measured. Goldfish were exposed to 200 μg/g β-sit (97% pure or as a 72.6% pure phytosterol mixture) and 10 μg/g 17β-estradiol (E2; 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 β-sit fish (p = 0.05) and E2-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 β-sit. This is the first study to show that β-sit has the capacity to alter gonadal StAR transcript abundance, offering a mechanism by which β-sit disrupts reproductive endocrine endpoints.