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Abstract
Multiple related cis-active elements required for cell-specific activation of the
rat prolactin gene appear to bind a pituitary-specific positive transcription factor(s),
referred to as Pit-1. DNA complementary to Pit-1 mRNA, cloned on the basis of specific
binding to AT-rich cell-specific elements in the rat prolactin and growth hormone
genes, encodes a 33 kd protein with significant similarity at its carboxyl terminus
to the homeodomains encoded by Drosophila developmental genes. Pit-1 mRNA is expressed
exclusively in the anterior pituitary gland in both somatotroph and lactotroph cell
types, which produce growth hormone and prolactin, respectively. Pit-1 expression
in heterologous cells (HeLa) selectively activates prolactin and growth hormone fusion
gene expression, suggesting that Pit-1 is sufficient to confer a characteristic pituitary
phenotype. The structure of Pit-1 and its recognition elements suggests that metazoan
tissue phenotype is controlled by a family of transcription factors that bind to related
cis-active elements and contain several highly conserved domains.