EXPRESSION OF PIT-1 AND RELATED PROTEINS IN DIVERSE HUMAN PITUITARY-ADENOMAS

Pit-1, a member of the POU family of homeodomain transcription factors , activates prolactin and GH gene expression but also has a role in pi tuitary cell differentiation and proliferation. Expression of Pit-1 ma y therefore be of central importance in the function and phenotype of human pituitary adenomas. We have found evidence that, in addition to Pit-1 mRNA, Pit-1-like immunoreactivity and DNA-binding activity are r eadily detectable in a series of human pituitary adenomas. Gel mobilit y shift assays using adenoma protein extracts with two Pit-1-binding s ites from the human prolactin promoter demonstrated the formation of s everal DNA sequence-specific protein-DNA complexes; some of these coul d be accounted for by Oct-1-binding activity. Pit-1 activity was antic ipated in prolactin- and GH-secreting adenomas, but was also detected in a proportion of endocrine-inactive (non-secreting) adenomas that di d not express Pit-1 target genes. The data demonstrate the presence of Pit-1 in a range of pituitary adenomas. Different adenomas generated slightly differing patterns of DNA-binding binding activity, though Pi t-1 mRNA and protein size appeared normal in all tumours so far examin ed.