Functional and distribution studies of isoforms of the pituitary-specific transcription factor, Pit-1.
Item
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Title
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Functional and distribution studies of isoforms of the pituitary-specific transcription factor, Pit-1.
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Identifier
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AAI9530889
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identifier
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9530889
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Creator
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Kloss, Brian.
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Contributor
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Adviser: Carter Bancroft
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Date
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1995
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Cell | Biology, Molecular | Biology, Animal Physiology
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Abstract
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The pituitary-specific transcription factor Pit-1 (GHF-1, Pit-1{dollar}\alpha{dollar}) has been shown to be involved in cell type-specific expression and hormonal regulation of the prolactin and growth hormone genes. Two unique protein products of the pit-1 gene, Pit-1a (GHF-2, Pit-1{dollar}\beta{dollar}) and {dollar}\Delta{dollar}4Pit-1, have been identified. The transcript encoding the Pit-1a isoform arises by alternate splicing of the Pit-1 mRNA precursor and is detected in all rat anterior pituitary cell lines examined. While Pit-1a binds the same regions of the rat prolactin and growth hormone gene proximal promoters as Pit-1, it is unable to trans-activate the prolactin gene promoter, yet it can trans-activate the growth hormone gene promoter. The {dollar}\Delta{dollar}4Pit-1 transcript is identical in sequence to Pit-1 except that it lacks exon IV of the pit-1 gene, encoding amino acids 147-201. Therefore, like Pit-1a, {dollar}\Delta{dollar}4Pit-1 is proposed to arise as a result of alternate splicing of the Pit-1 precursor mRNA. The excised amino acids of {dollar}\Delta{dollar}4Pit-1 represent a majority of the Pit-1 POU{dollar}\sb{lcub}\rm specific{rcub}{dollar} domain, necessary for homo- and heterodimerization and sequence-specific, high-affinity DNA binding. The {dollar}\Delta{dollar}4Pit-1 mRNA and protein are detected only in the GH{dollar}\sb3{dollar} somatomammotroph cell line and the {dollar}\Delta{dollar}4Pit-1 protein cannot bind DNA or trans-activate the prolactin and growth hormone gene promoters. Using an extremely sensitive amplification technique, it has been demonstrated that the 235-1 and MMQ cell lines contain readily detectable prolactin mRNA, but no detectable growth hormone mRNA and therefore appear to be true representatives of the mammotroph cell type. Taken together, these data suggest that in addition to Pit-1, the Pit-1a and {dollar}\Delta{dollar}4Pit-1 isoforms contribute to restrict expression of the prolactin and growth hormone genes to the appropriate cell types. However, the true functional roles of Pit-1a and {dollar}\Delta{dollar}4Pit-1 have yet to be determined.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
