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Effects of estrogen on esophageal function through regulation of Ca2+-related proteins

  • Original Article-Alimentary Tract
  • Published:
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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.

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Abbreviations

CaBP-9k:

S100 calcium binding protein G, Calbindin-D9k

PMCA1:

Plasma membrane Ca2+ ATPase

NCX1:

Sodium-calcium exchanger 1

E2:

17β –estradiol

P4:

Progesterone

ICI:

ICI 182,780

RU:

Mifepristone, RU486

ERα:

Estrogen receptor-alpha

MUC2:

Mucin 2

MYLK:

Myosin light chain kinase

BW:

Body wegiht

PND:

Postnatal day

DAPI:

4′,6-diamidino-2-phenylindole

AB-PAS:

Alcian blue-periodic acid-Schiff

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) Grant of Korean Government (MEST) (Nos. 2013-010514 and 2015R1A6A1A04020885).

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Authors and Affiliations

  1. Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea

    Kipung Kim, Dongoh Lee, Changhwan Ahn, Hee Young Kang & Eui-Bae Jeung

  2. 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

    Beum-Soo An

  3. Laboratory of Pharmacology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea

    Yeon Hee Seong

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  1. Kipung Kim
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Kim, K., Lee, D., Ahn, C. et al. Effects of estrogen on esophageal function through regulation of Ca2+-related proteins. J Gastroenterol 52, 929–939 (2017). https://doi.org/10.1007/s00535-016-1305-y

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