Function of the homeodomain protein GHF1 in pituitary cell proliferation.
Mutations that cause pituitary dwarfism in the mouse reside in the gene encoding the transcription factor growth hormone factor 1 (GHF1 or pit1). These dwarf mice (dw and dwJ) are deficient in growth hormone (GH) and prolactin (PRL) synthesis and exhibit pituitary hypoplasia, suggesting a stem cell defect. With antisense oligonucleotide technology, a cell culture model of this genetic defect was developed. Specific inhibition of GHF1 synthesis by complementary oligonucleotides led to a marked decrease in GH and PRL expression and to a marked decrease in proliferation of somatotrophic cell lines. These results provide direct evidence that the homeodomain protein GHF1 is required not only for the establishment and maintenance of the differentiated phenotype but for cell proliferation as well.
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093.
J L
JL
Castrillo
L E
LE
Theill
M
M
Karin
D000818:Animals; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000502:physiology*; D004392:Dwarfism / Q000235:genetics; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D013006:Growth Hormone / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000166:cytology* / Q000502:physiology; D011388:Prolactin / Q000235:genetics; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000502:physiology*
D016375:Antisense Elements (Genetics); D004247:DNA; D004268:DNA-Binding Proteins; D013006:Growth Hormone; D011388:Prolactin; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494185:Pou1f1 protein, mouse