Characterization of transiently and constitutively expressed progesterone receptors: Evidence for two functional states

Catharine Smith, Ronald G. Wolford, Tara B. O'Neill, Gordon L. Hager

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Activated steroid receptors induce chromatin remodeling events in the promoters of some target genes. We previously reported that transiently expressed progesterone receptor (PR) cannot activate mouse mammary tumor virus (MMTV) promoter when it adopts the form of ordered chromatin. However, when expressed continuously, the PR acquires this ability. In this study we explored whether this gain of function occurs through alterations in nucleoprotein structure at the MMTV promoter or through changes in receptor status. We observed no major structural differences at the MMTV promoter in the presence of constitutively expressed PR and found its mechanism of activation to be very similar to that of the glucocorticoid receptor (GR). However, a systematic comparison of the functional behavior of the transiently and constitutively expressed PR elucidated significant differences. The transiently expressed PR is activated in the absence of ligand by cAMP and by components in FBS and has significantly increased sensitivity to progestins. In contrast, the constitutively expressed PR is refractory to activation by cAMP and serum and has normal sensitivity to its ligand. In addition, while the PR is localized to the nucleus in both cases, a significant fraction of the transiently expressed PR is tightly bound to the nucleus even in the absence of ligand, while the majority of constitutively expressed PR is not. These results strongly suggest that the PR undergoes processing in the cell subsequent to its initial expression and that this processing is important for various aspects of its function, including its ability to productively interact with target genes that require chromatin remodeling for activation.

Original languageEnglish (US)
Pages (from-to)956-971
Number of pages16
JournalMolecular Endocrinology
Volume14
Issue number7
DOIs
StatePublished - 2000
Externally publishedYes

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Progesterone Receptors
Mouse mammary tumor virus
Carcinogens
Chromatin Assembly and Disassembly
Ligands
Nucleoproteins
Steroid Receptors
Glucocorticoid Receptors
Progestins
Genes
Chromatin

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Characterization of transiently and constitutively expressed progesterone receptors : Evidence for two functional states. / Smith, Catharine; Wolford, Ronald G.; O'Neill, Tara B.; Hager, Gordon L.

In: Molecular Endocrinology, Vol. 14, No. 7, 2000, p. 956-971.

Research output: Contribution to journalArticle

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