Characterisation of progestins used in hormonal contraception and progesterone via the progesterone receptor.
Dose-response
Efficacy
Potency
Progesterone
Progesterone receptor
Progestins
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
17 12 2020
17 12 2020
Historique:
received:
04
09
2020
accepted:
15
09
2020
pubmed:
4
10
2020
medline:
19
3
2021
entrez:
3
10
2020
Statut:
ppublish
Résumé
Different progestogens are widely used in hormonal therapy and mediate their therapeutic actions via the progesterone receptor (PR). Little published data exist on their relative efficacies and potencies via the PR, while those available may be confounded by off-target receptors, different methodologies and model systems. We performed dose-response analysis to investigate the efficacies and potencies for transcription of progesterone and several progestins widely used in contraception via the B isoform of human PR (PR-B). We compared responses using three different cell lines and two different transient transfection conditions. Results show that in vitro biological responses via PR-B for the select progestogens can vary significantly in biocharacter, rank order and absolute values for efficacies and potencies, depending on the cell line and transfection condition. Progestogen rank orders for published relative binding affinities are mostly different to those for relative efficacies and potencies. These in vitro differences suggest that rank orders and absolute values of the efficacies and potencies of the progestogens are likely to vary in vivo in a cell-specific and progestogen-specific manner, and cannot easily be extrapolated from in vitro data, as is usually the practice. While obtaining such data in vivo is not possible, these in vitro data show proof of concept for likely significant cell- and progestogen-specific PR-B effects.
Identifiants
pubmed: 33008590
pii: S0006-291X(20)31799-X
doi: 10.1016/j.bbrc.2020.09.058
pmc: PMC8129485
mid: NIHMS1693253
pii:
doi:
Substances chimiques
Contraceptive Agents, Hormonal
0
Progestins
0
Receptors, Progesterone
0
progesterone receptor B
0
Progesterone
4G7DS2Q64Y
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
879-885Subventions
Organisme : NICHD NIH HHS
ID : R01 HD083026
Pays : United States
Informations de copyright
Copyright © 2020 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. Please note that all Biochemical and Biophysical Research Communications authors are required to report the following potential conflicts of interest with each submission. If applicable to your manuscript, please provide the necessary declaration in the box above.
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