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Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function.

Publication ,  Journal Article
Vegeto, E; Shahbaz, MM; Wen, DX; Goldman, ME; O'Malley, BW; McDonnell, DP
Published in: Mol Endocrinol
October 1993

Two distinct isoforms of the human progesterone receptor (hPR-A and hPR-B) have been identified previously. They differ only in that hPR-B contains an additional 164 amino acids at the amino terminus. Among various species these two forms arise as a result of either alternate initiation of translation from the same mRNA or by transcription from alternate promoters within the same gene. In order to understand the reason for their existence, we studied the transcriptional capacity of these individual receptors and observed that their activity was influenced strongly by cell and promoter context. More surprising was the observation that in promoter and cell contexts where hPR-A was inactive, it acted as a potent trans-dominant repressor of hPR-B-mediated transcription. This event occurred at substoichiometric concentrations of hPR-A and was hormone dependent. Human PR-A was not a general repressor of ligand-mediated transcription, as it had no effect on vitamin D receptor function. Interestingly, hPR-A but not hPR-B was capable of a similar inhibition of glucocorticoid, androgen, and mineralocorticoid receptor-mediated gene transcription. This suggests a specific role for the hPR-A isoform in this regulatory process. The trans-dominant effects of hPR-A were induced also by the antiprogestins ZK112993 and ZK98299 and a DNA binding defective hPR-A mutant, suggesting that the inhibitory function of hPR-A does not require DNA binding. The dual role of hPR-A as an activator or repressor of transcription defines a potential mechanism by which cells can generate dissimilar responses to a single hormone and provides a molecular explanation for the existence of two distinct forms of the hPR.

Duke Scholars

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

October 1993

Volume

7

Issue

10

Start / End Page

1244 / 1255

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Transcription, Genetic
  • Receptors, Progesterone
  • Receptors, Mineralocorticoid
  • Receptors, Glucocorticoid
  • Receptors, Androgen
  • Promoter Regions, Genetic
  • Progesterone
  • Mammary Tumor Virus, Mouse
 

Citation

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Vegeto, E., Shahbaz, M. M., Wen, D. X., Goldman, M. E., O’Malley, B. W., & McDonnell, D. P. (1993). Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function. Mol Endocrinol, 7(10), 1244–1255. https://doi.org/10.1210/mend.7.10.8264658
Vegeto, E., M. M. Shahbaz, D. X. Wen, M. E. Goldman, B. W. O’Malley, and D. P. McDonnell. “Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function.Mol Endocrinol 7, no. 10 (October 1993): 1244–55. https://doi.org/10.1210/mend.7.10.8264658.
Vegeto E, Shahbaz MM, Wen DX, Goldman ME, O’Malley BW, McDonnell DP. Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function. Mol Endocrinol. 1993 Oct;7(10):1244–55.
Vegeto, E., et al. “Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function.Mol Endocrinol, vol. 7, no. 10, Oct. 1993, pp. 1244–55. Pubmed, doi:10.1210/mend.7.10.8264658.
Vegeto E, Shahbaz MM, Wen DX, Goldman ME, O’Malley BW, McDonnell DP. Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function. Mol Endocrinol. 1993 Oct;7(10):1244–1255.

Published In

Mol Endocrinol

DOI

ISSN

0888-8809

Publication Date

October 1993

Volume

7

Issue

10

Start / End Page

1244 / 1255

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Transcription, Genetic
  • Receptors, Progesterone
  • Receptors, Mineralocorticoid
  • Receptors, Glucocorticoid
  • Receptors, Androgen
  • Promoter Regions, Genetic
  • Progesterone
  • Mammary Tumor Virus, Mouse