The human progesterone receptor A-form functions as a transcriptional modulator of mineralocorticoid receptor transcriptional activity.
The human progesterone receptor (hPR) exists as two distinct molecular forms in most cells, hPR-A and -B. These receptor isoforms display distinct biological functions and demonstrate a cell and promoter specific ability to regulate gene transcription. In cellular contexts where hPR-A is transcriptionally inactive it can function as a ligand dependent inhibitor of mineralocorticoid receptor (MR) transcriptional activity. Inhibition occurs by a non-competitive mechanism as direct binding to MR is not required. Interestingly, PR agonists differ in their ability to facilitate the inhibitory function of hPR-A, suggesting that a specific receptor conformation may be preferred for this activity. Those compounds derived from 19-nor-testosterone are the most effective. The antiprogestins RU486, ZK98299 and ZK112993 are effective MR antagonists in the presence of coexpressed hPR-A. The mechanism of hPR-A mediated inhibition of MR transcriptional activity is unknown. We propose that inhibition results from a competition of hPR-A with MR for a common transcription factor and that the association of hPR-A with this factor is not transcriptionally productive.
Duke Scholars
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Related Subject Headings
- Transcription, Genetic
- Repressor Proteins
- Receptors, Progesterone
- Receptors, Mineralocorticoid
- Progestins
- Molecular Conformation
- Mineralocorticoid Receptor Antagonists
- Mifepristone
- Humans
- Haplorhini
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription, Genetic
- Repressor Proteins
- Receptors, Progesterone
- Receptors, Mineralocorticoid
- Progestins
- Molecular Conformation
- Mineralocorticoid Receptor Antagonists
- Mifepristone
- Humans
- Haplorhini