The human progesterone receptor A-form functions as a transcriptional modulator of mineralocorticoid receptor transcriptional activity.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • McDonnell, DP; Shahbaz, MM; Vegeto, E; Goldman, ME

Published Date

  • April 1, 1994

Published In

Volume / Issue

  • 48 / 5-6

Start / End Page

  • 425 - 432

PubMed ID

  • 8180103

Pubmed Central ID

  • 8180103

International Standard Serial Number (ISSN)

  • 0960-0760

Digital Object Identifier (DOI)

  • 10.1016/0960-0760(94)90190-2

Language

  • eng

Conference Location

  • England