title: Effects of estrogen on esophageal function through regulation of Ca2+-related proteins.
abstract: BACKGROUND
  The calcium ion is important for physiological functions in all tissues and organs and essential to many vital functions, including hormone secretion and muscle contraction. The intracellular concentration of calcium is regulated by calcium related proteins such as CaBP-9k, PMCA1, and NCX1. In this study, we investigated the relationship between calcium regulation and esophageal functions such as mucin secretion and smooth muscle contraction.
  
  
  METHODS
  To evaluate the influence of sex steroid hormones, immature rats were treated for 3 days with estradiol (E2), progesterone (P4), and their antagonists (ICI 182,780, and RU486). Esophageal function, transcription level, and localization of CaBP-9k, PMCA1, NCX1, ERα, and MUC2 were examined in the esophagus.
  
  
  RESULTS
  Transcriptional level of Cabp-9k and Muc2 was increased by E2, but not by P4. CaBP-9k, PMCA1, and MUC2 were mainly localized in the mucosal layer. Acidic mucosubstances in the esophagus were increased by E2 and recovered by ICI treatment. Unlike the expression of Cabp-9k, mRNA levels of Pmca1, Ncx1, and Erα were only decreased in response to E2, and recovered by ICI co-treatment group. The contraction of the esophagus and mRNA level of Mylk were reduced by E2. Overall, E2 upregulated mucus secretion, but downregulated muscle contraction in the esophagus through regulation of the expression of calcium related genes and the resultant intracellular calcium level.
  
  
  CONCLUSIONS
  The regulation of E2 in the function of esophagus may be applied to treat esophageal diseases such as reflux esophagitis, achalasia, and esophageal cancer.
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.
authors.forename: Kipung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.
authors.forename: Dongoh
authors.initials: D
authors.lastname: Lee
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.
authors.forename: Changhwan
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Kang
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Gyeongnam, 50463, Republic of Korea.
authors.forename: Beum-Soo
authors.initials: BS
authors.lastname: An
authors.affiliation: Laboratory of Pharmacology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Seong
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea. ebjeung@chungbuk.ac.kr.
authors.forename: Eui-Bae
authors.identifier: http://orcid.org/0000-0001-8936-916X
authors.initials: EB
authors.lastname: Jeung
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects*; D015735:Mifepristone / Q000494:pharmacology; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism; D009077:Mucins / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; C524628:Muc2 protein, rat; D055262:Mucin-2; D009077:Mucins; D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D000077267:Fulvestrant; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D053499:Plasma Membrane Calcium-Transporting ATPases; C506955:Atp2b1 protein, rat; D002118:Calcium
keywords: Calbindin-D9k; Esophagus; Estrogen; NCX1; PMCA1