Differential roles for signal transducers and activators of transcription 5a and 5b in PRL stimulation of ERα and ERβ transcription

Jonna Frasor, Kyungsoo Park, Michael Byers, Carlos Telleria, Toshio Kitamura, Li Yuan Yu-Lee, Jean Djiane, Ok Kyong Park-Sarge, Geula Gibori

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

PRL has been shown to stimulate mRNA expression of both ERα and ERβ in the rat corpus luteum and decidua of pregnancy. To investigate whether PRL may stimulate ER expression at the level of transcription and which transcription factors may mediate this stimulation, we have cloned the 5′-flanking regions of both rat ER genes. A constitutively active PRL receptor (PRL-RCA) stimulated both ERα and ERβ promoter activity, indicating that PRL is acting to stimulate ER transcription. Putative signal transducer and activator of transcription (Stat)5 response elements were identified at -189 in the ERα promoter and at -330 in the ERβ promoter. Mutation of these response elements or overexpression of dominant negative Stat5 prevented stimulation of ERα and ERβ promoter activity, indicating that PRL regulation of ER expression requires both intact Stat5 binding sites as well as functional Stat5. Interestingly, either Stat5a or Stat5b could stimulate ERα transcription while stimulation of ERβ occurred only in the presence of Stat5b. Through mutational analysis, a single nucleotide difference between the ERα and ERβ Stat5 response elements was shown to be responsible for the lack of Stat5a-mediated stimulation of ERβ. These findings indicate that PRL stimulation of ER expression occurs at the level of transcription and that PRL regulation of ERα can be mediated by either Stat5a or Stat5b, while regulation of ERβ appears to be mediated only by Stat5b.

Original languageEnglish
Pages (from-to)2172-2181
Number of pages10
JournalMolecular Endocrinology
Volume15
Issue number12
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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