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)
Haugen
B R
BR
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Gordon
D F
DF
Nelson
A R
AR
Wood
W M
WM
Ridgway
E C
EC
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010903:Pituitary Gland, Anterior; D011388:Prolactin / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology; D013972:Thyrotropin / Q000235:genetics*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D013006:Growth Hormone; D011388:Prolactin; D013972:Thyrotropin; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494185:Pou1f1 protein, mouse