Regulation of insulin-like growth factor I transcription by prostaglandin E2 in osteoblast cells

J. M. Pash, A. M. Delany, Martin L Adamo, C. T. Roberts, D. LeRoith, E. Canalis

Research output: Contribution to journalArticle

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Abstract

Insulin-like growth factor I (IGF-I) is a widely expressed abundant autocrine and paracrine factor that regulates the proliferation and differentiation of a variety of cell types. Prostaglandin E2 (PGE2) is a potent stimulator of IGF-I synthesis in bone. We examined the regulation of IGF-I synthesis by PGE2 in osteoblast-enriched (Ob) cells from fetal rat calvaria. PGE2 treatment of Ob cells at 1 μM for 2 h resulted in a 5-fold increase in heterogeneous nuclear RNA levels, as measured by a reverse transcriptase-polymerase chain reaction assay, suggesting an increase in IGF- I gene transcription. RNase protection analysis was used to map the transcriptional start sites in the IGF-I gene that are used in Ob cells. Consistent with other extrahepatic tissues, initiation of transcription occurs primarily at three sites within the 5'-regions of exon 1 of the IGF-I gene. PGE2 treatment did not alter start site usage. The regions upstream of these transcriptional start sites were analyzed by transiently transfecting Ob cells with putative rat IGF-I promoter sequences ligated to a luciferase reporter gene. Constructs containing 1.4 kilobases of the 5'-regions of exons 1 and 2 had significant promoter activity. PGE2 treatment of transfected Ob cells increased luciferase activity 5-fold when a 1.4-kilobase exon 1 promoter fragment was tested. This increase in luciferase activity was time and dose dependent. Smaller regions of the exon 1 promoter sequence gave higher basal activity and were less responsive to PGE2. We conclude that regions involved in IGF-I regulation by PGE2 are contained within the IGF-I promoter.

Original languageEnglish (US)
Pages (from-to)33-38
Number of pages6
JournalEndocrinology
Volume136
Issue number1
StatePublished - 1995

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Osteoblasts
Insulin-Like Growth Factor I
Dinoprostone
Exons
Luciferases
Heterogeneous Nuclear RNA
Genes
Ribonucleases
Reverse Transcriptase Polymerase Chain Reaction
Reporter Genes
Skull
Bone and Bones

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Pash, J. M., Delany, A. M., Adamo, M. L., Roberts, C. T., LeRoith, D., & Canalis, E. (1995). Regulation of insulin-like growth factor I transcription by prostaglandin E2 in osteoblast cells. Endocrinology, 136(1), 33-38.

Regulation of insulin-like growth factor I transcription by prostaglandin E2 in osteoblast cells. / Pash, J. M.; Delany, A. M.; Adamo, Martin L; Roberts, C. T.; LeRoith, D.; Canalis, E.

In: Endocrinology, Vol. 136, No. 1, 1995, p. 33-38.

Research output: Contribution to journalArticle

Pash, JM, Delany, AM, Adamo, ML, Roberts, CT, LeRoith, D & Canalis, E 1995, 'Regulation of insulin-like growth factor I transcription by prostaglandin E2 in osteoblast cells', Endocrinology, vol. 136, no. 1, pp. 33-38.
Pash JM, Delany AM, Adamo ML, Roberts CT, LeRoith D, Canalis E. Regulation of insulin-like growth factor I transcription by prostaglandin E2 in osteoblast cells. Endocrinology. 1995;136(1):33-38.
Pash, J. M. ; Delany, A. M. ; Adamo, Martin L ; Roberts, C. T. ; LeRoith, D. ; Canalis, E. / Regulation of insulin-like growth factor I transcription by prostaglandin E2 in osteoblast cells. In: Endocrinology. 1995 ; Vol. 136, No. 1. pp. 33-38.
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