RT Journal Article
SR Electronic
T1 Mutation of the POU-Specific Domain of Pit-1 and Hypopituitarism Without Pituitary Hypoplasia
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1118
OP 1121
DO 10.1126/science.257.5073.1118
VO 257
IS 5073
A1 Pfäffle, R. W.
A1 DiMattia, G. E.
A1 Parks, J. S.
A1 Brown, M. R.
A1 Wit, J. M.
A1 Jansen, M.
A1 Van der Nat, H.
A1 Van den Brande, J. L.
A1 Rosenfeld, M. G.
A1 Ingraham, H. A.
YR 1992
UL http://science.sciencemag.org/content/257/5073/1118.abstract
AB A point mutation in the POU-specific portion of the human gene that encodes the tissuespecific POU-domain transcription factor, Pit-1, results in hypopituitarism, with deficiencies of growth hormone, prolactin, and thyroid-stimulating hormone. In two unrelated Dutch families, a mutation in Pit-1 that altered an alanine in the first putative α helix of the POU-specific domain to proline was observed. This mutation generated a protein capable of binding to DNA response elments but unable to effectively activate its known target genes, growth hormone and prolactin. The phenotype of the affected individuals suggests that the mutant Pit-1 protein is competent to initiate other programs of gene activation required for normal proliferation of somatotrope, lactotrope, and thyrotrope cell types. Thus, a mutation in the POU-specific domain of Pit-1 has a selective effect on a subset of Pit-1 target genes.