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A R Nelson

Publications and source records attributed to A R Nelson.

At least 19 recordsLinked to original sources
PubMed1994

The combination of Pit-1 and Pit-1T have a synergistic stimulatory effect on the thyrotropin beta-subunit promoter but not the growth hormone or prolactin promoters.

Pit-1 is a pituitary-specific transcription factor with protein expression limited to thyrotrope, somatotrope, and lactotrope cells of the anterior pituitary gland. We have recently described a thyrotrope-specific variant isoform of Pit-1, called Pit-1T, which contains an additional 14 amino acids in the activation domain generated by an alternate 3'-splicing choice. Pit-1T, in the presence of Pit-1, stimulates the thyrotropin beta-subunit (TSH beta) promoter in a thyrotrope-derived cell that lacks all Pit-1 isoform proteins. Three laboratories have identified another Pit-1 splice variant, called Pit-1 beta, which contains an additional 26 amino acids in the activation domain that is generated by a similar 3'-alternate splice choice. Pit-1 beta has been shown to stimulate the GH promoter, but not the PRL or TSH beta promoters. In this report, we evaluate the effect of the three Pit-1 isoforms (Pit-1, Pit-1T, and Pit-1 beta) on the GH, PRL, and TSH beta promoters when introduced into different cell types. The combination of Pit-1 and Pit-1T had a synergistic stimulatory effect on the TSH beta promoter, but not on the PRL or GH promoters in a thyrotrope-derived cell line that lacks all Pit-1 protein isoforms (alpha TSH cells). When added to GH3 cells, which lack only the Pit-1T isoform, Pit-1T selectively stimulated the TSH beta promoter and not the GH or PRL promoters, suggesting that the thyrotrope-specific Pit-1T exhibits a promoter-specific effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternative Splicing↗
PubMed1993

Analysis of Pit-1 in regulating mouse TSH beta promoter activity in thyrotropes.

TSH beta gene expression is restricted to pituitary thyrotropes. Since Pit-1 is present in these cells, we characterized Pit-1 RNA and protein in thyrotropes, and tested its function in regulating TSH beta promoter activity. We demonstrate that both TtT-97 thyrotropic tumors and pituitaries contain four Pit-1 transcripts of 3.2, 2.6, 2.4, and 1.9 kb, respectively. Only two transcripts of 2.7 and 2.1 kb were detected in alpha TSH cells, a thyrotrope derived cell that no longer expresses TSH beta. Western analysis revealed Pit-1 protein in TtT-97 cells but not in alpha TSH cells. DNase I protection assays localized Pit-1 binding to three areas of the mouse TSH beta promoter. However, basal TSH beta promoter activity was minimally stimulated when alpha TSH cells or TtT-97 thyrotropes were co-transfected with mouse Pit-1 and a mTSH beta luciferase construct. These studies suggest that Pit-1 is not limiting for cell-specific expression of the TSH beta gene in thyrotrope-derived cells and implies that additional thyrotropic factors are likely required.

Animals↗