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Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect

  • Authors:
    • Othman A. Al‑Shboul
    • Mona S. Nazzal
    • Ayman G. Mustafa
    • Ahmed N. Al‑Dwairi
    • Mohammad A. Alqudah
    • Amal Abu Omar
    • Mahmoud A. Alfaqih
    • Mohammad I. Alsalem
  • View Affiliations / Copyright

    Affiliations: Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan, Department of Anatomy, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan, Department of Anatomy and Histology, Faculty of Medicine, Jordan University, Amman 11942, Jordan
    Copyright: © Al‑Shboul et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1685-1692
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    Published online on: July 4, 2018
       https://doi.org/10.3892/etm.2018.6406
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Abstract

Various gastrointestinal (GI) disorders have a higher prevalence in women than in men. In addition, estrogen has been demonstrated to have an inhibitory effect on the contractility of GI smooth muscle. Although increased plasma estrogen levels have been implicated in GI disorders, the role of gastric estrogen receptor (ER) in these sex‑specific differences remains to be fully elucidated. The present study was designed to investigate the sex‑associated differences in the expression of the two ER isoforms, ERα and ERβ, and the effect of estrogen on gastric muscle contraction via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. Experiments were performed on single gastric smooth muscle cells (GSMCs) isolated from male and female Sprague Dawley rats. The effect of acetylcholine (ACh), a muscarinic agonist, on the contraction of GSMCs was measured via scanning micrometry in the presence or absence of 1 µM 17β‑estradiol (E2), an agonist to the majority of ERs, 1,3,5‑tris(4‑hydroxyphenyl)‑4‑propyl‑1H‑pyrazole (PPT), an ERα agonist, or diarylpropionitrile (DPN), an ERβ agonist. The protein expression levels of ER subtypes in GSMCs were measured using a specifically designed ELISA. GSMCs from female rats had a higher expression of ERα and ERβ protein compared with GSMCs from males. ACh induced less contraction in female that in male GSMCs. Pre‑treatment of GSMCs with E2 reduced the contraction of GSMCs from both sexes, but to a greater extent in those from females. PPT and DPN inhibited ACh‑induced contraction in GSMCs from females. Furthermore, E2 increased NO and cGMP levels in GSMCs from males and females; however, higher levels were measured in females. Of note, pre‑incubation of female GSMCs with Nω‑nitro‑L‑arginine, a NO synthase inhibitor, or 1H‑[1,2,4]oxadiazolo[4,3‑a]quinoxalin‑1‑one, a guanylyl cyclase inhibitor, reduced the inhibitory effect of estrogen on GSMC contraction. In conclusion, estrogen relaxes GSMCs via an NO/cGMP‑dependent mechanism, and the reduced contraction in GSMCs from females by estrogen may be associated with the sex‑associated increased expression of ERα and ERβ, and greater production of NO and cGMP, compared with that in GSMCs from males.
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Copy and paste a formatted citation
Spandidos Publications style
Al‑Shboul OA, Nazzal MS, Mustafa AG, Al‑Dwairi AN, Alqudah MA, Abu Omar A, Alfaqih MA and Alsalem MI: Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect. Exp Ther Med 16: 1685-1692, 2018.
APA
Al‑Shboul, O.A., Nazzal, M.S., Mustafa, A.G., Al‑Dwairi, A.N., Alqudah, M.A., Abu Omar, A. ... Alsalem, M.I. (2018). Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect. Experimental and Therapeutic Medicine, 16, 1685-1692. https://doi.org/10.3892/etm.2018.6406
MLA
Al‑Shboul, O. A., Nazzal, M. S., Mustafa, A. G., Al‑Dwairi, A. N., Alqudah, M. A., Abu Omar, A., Alfaqih, M. A., Alsalem, M. I."Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect". Experimental and Therapeutic Medicine 16.3 (2018): 1685-1692.
Chicago
Al‑Shboul, O. A., Nazzal, M. S., Mustafa, A. G., Al‑Dwairi, A. N., Alqudah, M. A., Abu Omar, A., Alfaqih, M. A., Alsalem, M. I."Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect". Experimental and Therapeutic Medicine 16, no. 3 (2018): 1685-1692. https://doi.org/10.3892/etm.2018.6406
Copy and paste a formatted citation
x
Spandidos Publications style
Al‑Shboul OA, Nazzal MS, Mustafa AG, Al‑Dwairi AN, Alqudah MA, Abu Omar A, Alfaqih MA and Alsalem MI: Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect. Exp Ther Med 16: 1685-1692, 2018.
APA
Al‑Shboul, O.A., Nazzal, M.S., Mustafa, A.G., Al‑Dwairi, A.N., Alqudah, M.A., Abu Omar, A. ... Alsalem, M.I. (2018). Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect. Experimental and Therapeutic Medicine, 16, 1685-1692. https://doi.org/10.3892/etm.2018.6406
MLA
Al‑Shboul, O. A., Nazzal, M. S., Mustafa, A. G., Al‑Dwairi, A. N., Alqudah, M. A., Abu Omar, A., Alfaqih, M. A., Alsalem, M. I."Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect". Experimental and Therapeutic Medicine 16.3 (2018): 1685-1692.
Chicago
Al‑Shboul, O. A., Nazzal, M. S., Mustafa, A. G., Al‑Dwairi, A. N., Alqudah, M. A., Abu Omar, A., Alfaqih, M. A., Alsalem, M. I."Estrogen relaxes gastric muscle cells via a nitric oxide‑ and cyclic guanosine monophosphate‑dependent mechanism: A sex‑associated differential effect". Experimental and Therapeutic Medicine 16, no. 3 (2018): 1685-1692. https://doi.org/10.3892/etm.2018.6406
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