Defective retinoic acid regulation of the Pit-1 gene enhancer: A novel mechanism of combined pituitary hormone deficiency

Pit-1 is a pituitary-specific transcription factor responsible for pituitar y development and hormone expression in mammals. Pit-1 contains two protein domains, termed POU-specific and POU-homeo, which are both necessary for D NA binding and activation of the GH and PRL genes and regulation of the PRL , TSH-beta subunit (TSH-beta), and Pit-1 genes. Pit-1 is also necessary for retinoic acid induction of its own gene during development through a Pit-1 -dependent enhancer. Combined pituitary hormone deficiency is caused by def ective transactivation of target genes in the anterior pituitary. In the pr esent report, we provide in vivo evidence that retinoic acid induction of t he Pit-1 gene can be impaired by a Pit-1 gene mutation, suggesting a new mo lecular mechanism for combined pituitary hormone deficiency in man.