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Interrogating the estrogen-mediated regulation of adrenocortical Klotho expression using ovariectomized albino rat model exposed to repeated restraint stress

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Abstract

Reproductive aging is associated with altered stress response and many other menopausal symptoms. Little is known about the adrenal expression of the anti-aging protein Klotho or how it is modulated by estrogen in ovariectomized stressed rats. Fifty-six Wistar female rats were assigned into seven equal groups. Sham-operated (Sham), sham stressed (Sham/STS), ovariectomized (OVR), ovariectomized stressed (OVR/STS), ovariectomized stressed rosiglitazone-treated (OVR/STS/R), ovariectomized stressed estrogen-treated (OVR/STS/E), and ovariectomized stressed estrogen/GW9662 co-treated (OVR/STS/E/GW) groups. All stressed rats were subjected daily to a one-hour restraint stress test for 19 days. At the end of the experiment, blood was collected for serum corticosterone (CORT) analysis. Adrenal tissues were obtained and prepared for polymerase chain reaction (PCR) assay, hematoxylin and eosin (H&E), immunohistochemistry-based identification of Klotho and PPAR-γ, and Oil Red O (ORO) staining. The rise in serum CORT was negligible in the OVR/STS group, in contrast to the Sham/STS group. The limited CORT response in the former group was restored by estrogen and rosiglitazone and blocked by estrogen/GW9226 co-administration. ORO-staining revealed a more evident reduction in the adrenal fat in the OVR/STS group, which was reversed by estrogen and counteracted by GW. Also, there was a comparable expression pattern of Klotho and PPAR-γ in the adrenals. The adrenal Klotho decreased in the OVR/STS group, but was reversed by estrogen treatment. GW9226/estrogen co-treatment interfered with the regulatory effect of estrogen on Klotho. The study suggested modulation of the adrenal Kotho expression by estrogen, in the ovariectomized rats subjected to a restraint stress test. This estrogen-provided adrenal protection might be mediated by PPAR-γ activation.

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All the research data are present in the published version of the article, and further queries are on reasonable request.

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Acknowledgements

The authors extend their appreciation to the Researchers Supporting Project number (RSPD2024R759), King Saud University, Riyadh, Saudi Arabia.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Histology and Cell Biology, Faculty of Medicine, Fayoum University, Fayoum, 63511, Egypt

    Ahmed A. Morsi

  2. Biochemistry Department, Faculty of Science, Assiut University, 71515, Assiut, Egypt

    Ezat A. Mersal

  3. Physiology Department, Faculty of Medicine, Fayoum University, Fayoum, 63511, Egypt

    Ahmed M. Abdelmoneim

  4. Medical Ethics and Law, Department of Medical Education, School of Medicine, Trinity College Dublin, 152-160 Pearse St, Dublin, D02 R590, Ireland

    Ghaiath Hussein

  5. Department of Anatomy and Embryology, Faculty of Medicine, Fayoum University, Fayoum, 63511, Egypt

    Mohamed M. Sofii

  6. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Khalid Elfaki Ibrahim

  7. Medical Laboratory Technology Department, Higher Technological Institute of Applied Health Sciences, Beni-Suef, Egypt

    Mohamed S. Salim

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Contributions

Ahmed Morsi: Conceptualization, Methodology, formal analysis, Writing- Reviewing and Editing. Mohamed Salim: project administration, investigation, visualization, resources, and image photography. Ezat Mersal, Ahmed Abdelmoneim, and Mohamed Sofii: supervision, formal analysis, Writing—Original Draft, and resources. Ghaiath Hussein: Revision of the experimental procedures, ethical issues, and final review and editing. Khalid Ibrahim: data curation, validation, resources.

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Correspondence to Ahmed A. Morsi.

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The study proposal and the experimental procedures were approved by the Fayoum University Institutional Animal Care and Use Committee (FU-IACUC-AEC2343).

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Morsi, A.A., Mersal, E.A., Abdelmoneim, A.M. et al. Interrogating the estrogen-mediated regulation of adrenocortical Klotho expression using ovariectomized albino rat model exposed to repeated restraint stress. Human Cell (2024). https://doi.org/10.1007/s13577-024-01069-8

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