The Role of Estriol and Estrone in Keratoconic Stromal Sex Hormone Receptors

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dc.creatorEscandon, Paulina
dc.creatorNicholas, Sarah E.
dc.creatorCunningham, Rebecca L.
dc.creatorMurphy, David A.
dc.creatorRiaz, Kamran M.
dc.creatorKaramichos, Dimitrios
dc.creator.orcid0000-0002-8761-3824 (Karamichos, Dimitrios)
dc.creator.orcid0000-0001-5984-5516 (Cunningham, Rebecca)
dc.date.accessioned2022-09-20T20:19:47Z
dc.date.available2022-09-20T20:19:47Z
dc.date.issued2022-01-14
dc.description.abstractKeratoconus (KC) is a progressive corneal thinning disease that manifests in puberty and worsens during pregnancy. KC onset and progression are attributed to diverse factors that include: environmental, genetics, and hormonal imbalances; however, the pathobiology remains elusive. This study aims to determine the role of corneal stroma sex hormone receptors in KC and their interplay with estrone (E1) and estriol (E3) using our established 3D in vitro model. Healthy cornea stromal cells (HCFs) and KC cornea stromal cells (HKCs), both male and female, were stimulated with various concentrations of E1 and E3. Significant changes were observed between cell types, as well as between males and females in the sex hormone receptors tested; androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERalpha), and estrogen receptor beta (ERbeta) using Western blot analysis. E1 and E3 stimulations in HCF females showed AR, PR, and ERbeta were significantly upregulated compared to HCF males. In contrast, ERalpha and ERbeta had significantly higher expression in HKC's females than HKC's males. Our data suggest that the human cornea is a sex-dependent, hormone-responsive tissue that is significantly influenced by E1 and E3. Therefore, it is plausible that E1, E3, and sex hormone receptors are involved in the KC pathobiology, warranting further investigation.
dc.description.sponsorshipThe authors would like to acknowledge the following: National Eye Institute (NEI), National Institutes of Health (NIH) for the financial support (EY028888).
dc.identifier.citationEscandon, P., Nicholas, S. E., Cunningham, R. L., Murphy, D. A., Riaz, K. M., & Karamichos, D. (2022). The Role of Estriol and Estrone in Keratoconic Stromal Sex Hormone Receptors. International journal of molecular sciences, 23(2), 916. https://doi.org/10.3390/ijms23020916
dc.identifier.issn1422-0067
dc.identifier.issue2
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31794
dc.identifier.volume23
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/ijms23020916
dc.rights.holder© 2022 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceInternational Journal of Molecular Sciences
dc.subjectcornea
dc.subjectkeratoconus
dc.subjectsex hormones
dc.subject.meshBiomarkers
dc.subject.meshCells, Cultured
dc.subject.meshCorneal Stroma / metabolism
dc.subject.meshDisease Susceptibility
dc.subject.meshEstriol / metabolism
dc.subject.meshEstrogen Receptor alpha / metabolism
dc.subject.meshEstrogen Receptor beta / metabolism
dc.subject.meshEstrone / metabolism
dc.subject.meshGonadal Steroid Hormones / metabolism
dc.subject.meshHumans
dc.subject.meshKeratoconus / etiology
dc.subject.meshKeratoconus / metabolism
dc.subject.meshKeratoconus / pathology
dc.subject.meshReceptors, Androgen / metabolism
dc.subject.meshReceptors, Progesterone / metabolism
dc.subject.meshReceptors, Steroid / metabolism
dc.titleThe Role of Estriol and Estrone in Keratoconic Stromal Sex Hormone Receptors
dc.typeArticle
dc.type.materialtext

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