title: Estrogen-responsive genes encoding egg yolk proteins vitellogenin and apolipoprotein II in chicken are differentially regulated by selective estrogen receptor modulators.
abstract: In a hen, large quantities of the egg yolk proteins, apolipoprotein II (apo-II) and vitellogenin (VG), are expressed in the liver and transported to the oviduct during egg production. Estrogenic stimulation of the hepatic expression of apo-II and VG is due to both transcriptional increase and mRNA stabilization. The nucleolytic degradation of apo-II messenger RNA (mRNA) is prevented by estrogen-regulated mRNA-stabilizing factor (E-RmRNASF). Gene-specific effects of a select panel of selective estrogen receptor modulators (SERMs) on the hepatic expression of the estrogen-responsive genes encoding apo-II, VG, and E-RmRNASF in the chicken liver were investigated. In the present study, 6-week-old roosters were treated with the vehicle, estrogen, the SERMs genistein, resveratrol, tamoxifen, pterostilbene, raloxifene, catechin, and clomiphene or a combination of estrogen and a 200-fold excess of each of the SERMs. Results from mRNA stabilization studies conducted to investigate the stimulation of expression of E-RmRNASF in the liver by these agents showed that the expression of E-RmRNASF in the liver was stimulated by estrogen and the SERMs genistein, resveratrol, tamoxifen, pterostilbene, and catechin but not by the vehicle, clomiphene or raloxifene. The expression of apo-II and VG from the aforementioned treatments was determined by Northern blot analysis, RNase protection assays, and Western blot analysis. The transcription and protein expression of both apo-II and VG genes were seen in response to treatment with estrogen but not with the SERMs or combinations of estrogen and each of the SERMs. The SERMs that stimulated the expression of E-RmRNASF antagonized the stimulation of the expression of both apo-II and VG by estrogen, demonstrating a gene-specific, selective regulation of the aforementioned genes in the chicken liver by the SERMs. The above panel of SERMs may likely have adverse effects on egg production.
authors.affiliation: Division of Pharmaceutical Sciences, Department of Pharmacology and Toxicology, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York, USA. Electronic address: wratna@liu.edu.
authors.forename: Warren N
authors.initials: WN
authors.lastname: Ratna
authors.affiliation: Division of Pharmaceutical Sciences, Department of Pharmacology and Toxicology, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York, USA.
authors.forename: Vrushank D
authors.initials: VD
authors.lastname: Bhatt
authors.affiliation: Division of Pharmaceutical Sciences, Department of Pharmacology and Toxicology, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York, USA.
authors.forename: Kawshik
authors.initials: K
authors.lastname: Chaudhary
authors.affiliation: Division of Pharmaceutical Sciences, Department of Pharmacology and Toxicology, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York, USA.
authors.forename: Ammar
authors.initials: A
authors.lastname: Bin Ariff
authors.affiliation: Division of Pharmaceutical Sciences, Department of Pharmacology and Toxicology, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York, USA.
authors.forename: Supriya A
authors.initials: SA
authors.lastname: Bavadekar
authors.affiliation: Division of Pharmaceutical Sciences, Department of Pharmacology and Toxicology, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York, USA.
authors.forename: Haran N
authors.initials: HN
authors.lastname: Ratna
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000235:genetics*; D015152:Blotting, Northern; D002645:Chickens / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004527:Egg Proteins; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D014819:Vitellogenins / Q000235:genetics*
chemical_list: D001053:Apolipoproteins; D004527:Egg Proteins; D004967:Estrogens; D011498:Protein Precursors; D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D014819:Vitellogenins; C054949:apolipoprotein II
keywords: Apolipoprotein II; E-RmRNASF; Estrogen; Gene specificity; Selective estrogen receptor modulators; Vitellogenin