title: Effect of sex hormones on n-3 polyunsaturated fatty acid biosynthesis in HepG2 cells and in human primary hepatocytes.
abstract: Female humans and rodents have been shown to have higher 22:6n-3 status and synthesis than males. It is unclear which sex hormone is involved. We investigated the specificity of the effects of physiological concentrations of sex hormones in vitro on the mRNA expression of genes involved in polyunsaturated fatty acid (PUFA) biosynthesis and on the conversion of [d5]-18:3n-3 to longer chain fatty acids. Progesterone, but not 17α-ethynylestradiol or testosterone, increased FADS2, FADS1, ELOVl 5 and ELOVl 2 mRNA expression in HepG2 cells, but only FADS2 in primary human hepatocytes. In HepG2 cells, these changes were accompanied by hypomethylation of specific CpG loci in the FADS2 promoter. Progesterone, not 17α-ethynylestradiol or testosterone, increased conversion of [d5]-18:3n-3 to 20:5n-3, 22:5n-3 and 22:6n-3. These findings show that progesterone increases n-3 PUFA biosynthesis by up-regulating the mRNA expression of genes involved in this pathway, possibly via changes in the epigenetic regulation of FADS2.
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Charlene M
authors.initials: CM
authors.lastname: Sibbons
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York, United States.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Brenna
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Lawrence
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Hoile
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Clarke-Harris
authors.affiliation: Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Lillycrop
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK. Electronic address: g.c.burdge@soton.ac.uk.
authors.forename: Graham C
authors.initials: GC
authors.lastname: Burdge
mesh_terms: D002478:Cells, Cultured; D000090943:Delta-5 Fatty Acid Desaturase; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000096:biosynthesis*; D005260:Female; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D061251:Primary Cell Culture; D011374:Progesterone / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D015525:Fatty Acids, Omega-3; D013739:Testosterone; D004997:Ethinyl Estradiol; D011374:Progesterone; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human
keywords: Docosahexaenoic acid; Eicosapentaenoic acid; Elongase; Estrogen; FADS; Omega-3 polyunsaturated fatty acids; Progesterone; Testosterone