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• W4288045401 endingPage "109094" @default.
• W4288045401 startingPage "109094" @default.
• W4288045401 abstract "Hormonal contraceptives (HCs) and hormone replacement therapy (HRT) are therapies designed to target the progesterone receptor (PR) to prevent unwanted pregnancy and to alleviate the symptoms of menopause, respectively, in women. Although these therapies are widely used globally, few studies have investigated in parallel how the transcriptional responses of the progestogens used in these therapies compare to each other via the PR isoforms (PR-A and PR-B). Using dose-response promoter-reporter and endogenous gene expression assays, we compared the transcriptional responses of six widely-used progestogens via each PR isoform. The present study shows that progestogens exhibit progestogen-specific potencies and efficacies via both PR isoforms. In addition, the endogenous gene expression data reveals that progestogens exhibit promoter-specific effects. Furthermore, this study reveals that progestogen responses via PR-A are significantly more potent and less efficacious than those observed via PR-B, and that this is unlikely due to differences in PR protein levels. Correlation analysis revealed that there is no detectable correlation between potency or efficacy of progestogens for PR-B or PR-A versus reported relative binding affinity (RBA) of progestogens for the PR, consistent with complex mechanisms of PR regulation. Taken together, our data show that it cannot be assumed that all progestogens have similar transcriptional responses on all genes. Since the PR plays a role in cognition, regulation of inflammation, mitochondrial function, neurogenesis, female reproduction and disease, the data suggest that these important physiological functions could be differentially affected depending on progestogen, promoter, and ratios of PR isoforms." @default.
• W4288045401 created "2022-07-27" @default.
• W4288045401 creator A5058466834 @default.
• W4288045401 creator A5067887867 @default.
• W4288045401 creator A5085798165 @default.
• W4288045401 date "2022-11-01" @default.
• W4288045401 modified "2023-10-18" @default.
• W4288045401 title "Progestogens exhibit progestogen-, promoter- and isoform-specific effects via the progesterone receptor" @default.
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• W4288045401 doi "https://doi.org/10.1016/j.steroids.2022.109094" @default.
• W4288045401 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35905833" @default.
• W4288045401 hasPublicationYear "2022" @default.
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