title: Suppressed Sex Hormone Biosynthesis by Alkylresorcinols: A Possible Link to Chemoprevention.
abstract: Alkylresorcinols (ARs, 5-n-alkylresorcinols) are amphiphilic phenolic lipids in whole grain rye and wheat, with a long odd-numbered carbon chain. A preventive effect of whole grain diet on sex hormone-dependent cancers has been recognized, but the active component(s) or mechanisms are not known. We have investigated the effects of the ARs C15:0, C19:0, and C21:0, individually and in combination, on steroid hormone production by using the human adrenocortical cell line H295R. Decreased synthesis of dehydroepiandrosterone (DHEA), testosterone, and estradiol was demonstrated at low concentrations of C15:0 and C19:0. There were no indications of additive effects on steroid secretion from the combined treatment with equimolar concentrations of the three ARs. Gene expressions of CYP21A2, HSD3B2, and CYP19A1 were downregulated and CYP11A1 was upregulated by the ARs. The results on gene expression could not explain the effects on steroidogenesis, which may be due to direct effects on enzyme activities, such as inhibition of CYP17A1. Our results demonstrate suppressed synthesis of testosterone and estradiol by ARs suggesting a novel mechanism for ARs in the chemoprevention of prostate and breast cancer.
authors.affiliation: a Department of Biomedical Sciences and Veterinary Public Health , Swedish University of Agricultural Sciences , Uppsala , Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Oskarsson
authors.affiliation: a Department of Biomedical Sciences and Veterinary Public Health , Swedish University of Agricultural Sciences , Uppsala , Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Ohlsson Andersson
mesh_terms: D000302:Adrenal Cortex / Q000201:enzymology / Q000378:metabolism*; D000478:Alkylation; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000378:metabolism*; D001141:Aromatase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019587:Dietary Supplements; D004958:Estradiol / Q000096:biosynthesis; D004965:Estrogen Antagonists / Q000737:chemistry / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D011375:Progesterone Reductase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012118:Resorcinols / Q000737:chemistry / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D016588:Anticarcinogenic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004965:Estrogen Antagonists; D005227:Fatty Acids; D012118:Resorcinols; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol; C117025:pentadecanoic acid; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; D001141:Aromatase; C561410:CYP19A1 protein, human; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; C517969:nonadecanoic acid; C517970:heneicosanoic acid