Progestogens exhibit progestogen-, promoter- and isoform-specific effects via the progesterone receptor.
Dose–response
Efficacy
Potency
Progesterone receptor
Progestins
Receptor isoforms
Journal
Steroids
ISSN: 1878-5867
Titre abrégé: Steroids
Pays: United States
ID NLM: 0404536
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
04
04
2022
revised:
13
07
2022
accepted:
23
07
2022
pubmed:
30
7
2022
medline:
19
10
2022
entrez:
29
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35905833
pii: S0039-128X(22)00132-5
doi: 10.1016/j.steroids.2022.109094
pmc: PMC9939308
mid: NIHMS1867184
pii:
doi:
Substances chimiques
Contraceptive Agents
0
Progesterone
4G7DS2Q64Y
Progestins
0
Protein Isoforms
0
Receptors, Progesterone
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
109094Subventions
Organisme : NICHD NIH HHS
ID : R01 HD083026
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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