TY - JOUR
T1 - Hormonal regulation of the thyrotropin β-subunit gene by phosphorylation of the pituitary-specific transcription factor Pit-1
AU - Steinfelder, Hans J.
AU - Radovick, Sally
AU - Wondisford, Fredric E.
PY - 1992/7/1
Y1 - 1992/7/1
N2 - The pituitary-specific transcription factor Pit-1 is a cell-specific activator of prolactin and growth hormone gene transcription in the anterior pituitary. Pit-1 has also been shown to mediate both thyrotropin-releasing hormone (TRH) and cAMP stimulation of the prolactin and thyrotropin β-subunit (TSHβ) genes. The molecular mechanism by which Pit-1 mediates these stimulatory effects remains unclear. At least three Pit-1-binding elements within the TSHβ gene mediate responsiveness to TRH and cAMP. The present studies were designed to test the hypothesis that phosphorylation is an important modulator of Pit-1 interaction with the TSHβ gene. TSHβ elements bind less well to nonphosphorylated Pit-1 than to phosphorylated Pit-1 and are weak activators of gene expression, unlike high-affinity Pit-1 binding sites in the prolactin and growth hormone genes. Phosphorylation by protein kinase A or C enhances Pit-1 binding to TSHβ elements 3- to 8-fold. Conversely, phosphorylation generally reduces binding of Pit-1 to elements within the prolactin and growth hormone genes. A variation within the consensus sequence for Pit-1 binding in TSHβ gene elements [A(A/T)(A/T)AATNCAT in the TSHβ gene versus A(A/T)(A/T)TATNCAT in the prolactin and growth hormone genes] could explain these differences. These elements may limit basal activation of the TSHβ gene by binding less well to nonphosphorylated Pit-1 while conferring hormonal stimulation through enhanced binding of phosphorylated Pit-1.
AB - The pituitary-specific transcription factor Pit-1 is a cell-specific activator of prolactin and growth hormone gene transcription in the anterior pituitary. Pit-1 has also been shown to mediate both thyrotropin-releasing hormone (TRH) and cAMP stimulation of the prolactin and thyrotropin β-subunit (TSHβ) genes. The molecular mechanism by which Pit-1 mediates these stimulatory effects remains unclear. At least three Pit-1-binding elements within the TSHβ gene mediate responsiveness to TRH and cAMP. The present studies were designed to test the hypothesis that phosphorylation is an important modulator of Pit-1 interaction with the TSHβ gene. TSHβ elements bind less well to nonphosphorylated Pit-1 than to phosphorylated Pit-1 and are weak activators of gene expression, unlike high-affinity Pit-1 binding sites in the prolactin and growth hormone genes. Phosphorylation by protein kinase A or C enhances Pit-1 binding to TSHβ elements 3- to 8-fold. Conversely, phosphorylation generally reduces binding of Pit-1 to elements within the prolactin and growth hormone genes. A variation within the consensus sequence for Pit-1 binding in TSHβ gene elements [A(A/T)(A/T)AATNCAT in the TSHβ gene versus A(A/T)(A/T)TATNCAT in the prolactin and growth hormone genes] could explain these differences. These elements may limit basal activation of the TSHβ gene by binding less well to nonphosphorylated Pit-1 while conferring hormonal stimulation through enhanced binding of phosphorylated Pit-1.
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U2 - 10.1073/pnas.89.13.5942
DO - 10.1073/pnas.89.13.5942
M3 - Article
C2 - 1321428
AN - SCOPUS:0026754225
SN - 0027-8424
VL - 89
SP - 5942
EP - 5945
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -