Regulation of prolactin receptor (PRLR) gene expression in insulin-producing cells. Prolactin and growth hormone activate one of the rat prlr gene promoters via STAT5a and STAT5b
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Regulation of prolactin receptor (PRLR) gene expression in insulin-producing cells. Prolactin and growth hormone activate one of the rat prlr gene promoters via STAT5a and STAT5b. / Galsgaard, E D; Møldrup, Annette; Nielsen, Jens Høiriis.
I: The Journal of Biological Chemistry, Bind 274, Nr. 26, 25.06.1999, s. 18686-92.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Regulation of prolactin receptor (PRLR) gene expression in insulin-producing cells. Prolactin and growth hormone activate one of the rat prlr gene promoters via STAT5a and STAT5b
AU - Galsgaard, E D
AU - Møldrup, Annette
AU - Nielsen, Jens Høiriis
PY - 1999/6/25
Y1 - 1999/6/25
N2 - Expression of the prolactin receptor (PRLR) gene is increased in pancreatic islets during pregnancy and in vitro in insulin-producing cells by growth hormone (GH) and prolactin (PRL). The 5'-region of the rat PRLR gene contains at least three alternative first exons that are expressed tissue-specifically because of differential promoter usage. We show by reverse transcription-polymerase chain reaction analysis that both exon 1A- and exon 1C-containing PRLR transcripts are expressed in rat islets and that human (h)GH, ovine (o)PRL, and bovine (b)GH increase exon 1A expression 6.5 +/- 0. 8-fold, 6.8 +/- 0.7-fold, and 3.9 +/- 0.7-fold and exon 1C expression 4.8 +/- 0.4-fold, 4.4 +/- 0.6-fold, and 2.5 +/- 0.7-fold, respectively. Expression of exon 1B was not detectable. The transcriptional activities of reporter constructs containing the 1A, 1B, or 1C promoter were found to be 22.8-fold, 2.7-fold, and 8. 0-fold, respectively, above that of a promoterless reporter construct when transfected into the insulin-producing INS-1 cells. The transcriptional activity of the 1A promoter construct was increased 8.9 +/- 1.9-fold by 0.5 microgram/ml hGH. Responsiveness to hGH of the 1A promoter was localized to the region from -225 to +81 with respect to the transcription start site. This region contains the sequence TTCTAGGAA that by gel retardation experiments was shown to bind the transcription factors STAT5a and STAT5b in response to stimulation by hGH, oPRL, or bGH. Mutation of this gamma-activated sequence-like element completely abolished transcriptional induction of the 1A promoter by hGH. Our results suggest that GH and PRL increase the levels of exon 1A- and 1C-containing PRLR mRNA species and furthermore that the transcriptional activity of the 1A promoter is increased via activation of STAT5a and STAT5b.
AB - Expression of the prolactin receptor (PRLR) gene is increased in pancreatic islets during pregnancy and in vitro in insulin-producing cells by growth hormone (GH) and prolactin (PRL). The 5'-region of the rat PRLR gene contains at least three alternative first exons that are expressed tissue-specifically because of differential promoter usage. We show by reverse transcription-polymerase chain reaction analysis that both exon 1A- and exon 1C-containing PRLR transcripts are expressed in rat islets and that human (h)GH, ovine (o)PRL, and bovine (b)GH increase exon 1A expression 6.5 +/- 0. 8-fold, 6.8 +/- 0.7-fold, and 3.9 +/- 0.7-fold and exon 1C expression 4.8 +/- 0.4-fold, 4.4 +/- 0.6-fold, and 2.5 +/- 0.7-fold, respectively. Expression of exon 1B was not detectable. The transcriptional activities of reporter constructs containing the 1A, 1B, or 1C promoter were found to be 22.8-fold, 2.7-fold, and 8. 0-fold, respectively, above that of a promoterless reporter construct when transfected into the insulin-producing INS-1 cells. The transcriptional activity of the 1A promoter construct was increased 8.9 +/- 1.9-fold by 0.5 microgram/ml hGH. Responsiveness to hGH of the 1A promoter was localized to the region from -225 to +81 with respect to the transcription start site. This region contains the sequence TTCTAGGAA that by gel retardation experiments was shown to bind the transcription factors STAT5a and STAT5b in response to stimulation by hGH, oPRL, or bGH. Mutation of this gamma-activated sequence-like element completely abolished transcriptional induction of the 1A promoter by hGH. Our results suggest that GH and PRL increase the levels of exon 1A- and 1C-containing PRLR mRNA species and furthermore that the transcriptional activity of the 1A promoter is increased via activation of STAT5a and STAT5b.
KW - Animals
KW - Cattle
KW - Cells, Cultured
KW - DNA-Binding Proteins
KW - Enhancer Elements, Genetic
KW - Exons
KW - Female
KW - Gene Expression Regulation
KW - Growth Hormone
KW - Humans
KW - Insulin
KW - Islets of Langerhans
KW - Milk Proteins
KW - Mutagenesis, Site-Directed
KW - Pregnancy
KW - Prolactin
KW - Promoter Regions, Genetic
KW - Rats
KW - Rats, Wistar
KW - Receptors, Prolactin
KW - STAT5 Transcription Factor
KW - Trans-Activators
KW - Tumor Suppressor Proteins
M3 - Journal article
C2 - 10373481
VL - 274
SP - 18686
EP - 18692
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 26
ER -
ID: 47972652