129 Selenium-form affects de novo cholesterol synthesis and catabolism of cholesterol and progesterone in the liver of beef heifers

Abstract

Abstract A deficiency of selenium (Se) in soils and hence forages poses a challenge to producers in the southeast United States, necessitating supplementation of this trace mineral to the diet of pasture fed cattle. Se occurs in either inorganic (ISe) or organic (OSe) forms; ISe is conventionally available in commercial supplements, while OSe is available in grazed forages. We have investigated supplementation with either ISe or a 1:1 mixture of ISe:OSe (MIX) and demonstrated that MIX increases the relative abundance of mRNA encoding the low-density lipoprotein receptor (LDLR) and enzymes involved in de novo cholesterol synthesis in the corpus luteum, concurrent with a MIX-induced increase in systemic progesterone (P4) during the early luteal phase. We also observed a MIX-induced decrease in circulating cholesterol and low-density/very low-density lipoproteins during early gestation, and a MIX-induced increase in conceptus length at maternal recognition of pregnancy (MRP). The objective herein was to investigate the effect of form of Se (ISe versus MIX) on de novo cholesterol synthesis and cholesterol/steroid catabolism in the liver at MRP. We hypothesized form of Se would affect the abundance of transcripts that regulate synthesis, catabolism, and local concentrations of cholesterol and P4. Angus-cross heifers were supplemented with ISe or MIX for at least 90 d before insemination at observed estrus. On d 17 of pregnancy, heifers (n = 6/TRT) were killed and their reproductive tracts and conceptuses recovered. Hepatic samples were collected for qPCR analysis of mRNA transcripts encoding proteins involved in de novo cholesterol synthesis, regulation of cholesterol availability and steroid catabolism. Additionally, on d 7 and d 17 of pregnancy, we quantified systemic concentrations of high-density lipoproteins (HDL), indicative of cholesterol recycling to the liver. We quantified the relative abundance of 22 mRNAs and observed that heifers supplemented with MIX-form Se had an increase in the relative abundance of mRNA encoding the very low-density lipoprotein receptor (VLDLR, P = 0.01). Unexpectedly, we failed to detect an effect of TRT on the abundance of mRNA encoding the high-density lipoprotein receptor (SCARB1, P > 0.05) which was consistent with our inability to detect an effect on the serum concentration of total or free HDL (P > 0.05) during early pregnancy and at MRP. Of the 11 mRNA transcripts encoding enzymes involved in catabolism of cholesterol and progesterone, including steroid alpha reductases (SRD5A1 and SRD5A3) and cytochrome P450 enzymes (CYP4A2, CYP4A11, CYP11A1, and CYP17A1), we were unable to detect a difference in the relative abundance of any transcript. Overall, it appears that the form of Se is altering circulating concentrations of cholesterol and further affecting whole animal physiology and fertility; however, the mechanism involved remains to be fully elucidated and warrants further investigation.