The GHRH receptor is expressed in the somatotroph cell of the anterior pituitary where it functions to mediate GHRH-stimulated GH release. To study pituitary and somatotroph cell-specific expression of this gene, a transgenic mouse model and complimentary cell culture experiments were developed. The activity of the 1.6kb proximal rat GHRH receptor promoter was examined in vivo by generating transgenic mice with the promoter directing expression of a luciferase reporter. The promoter directs tissue-specific expression, as luciferase is highly expressed in the pituitary, but absent from fourteen other tissues. Immunocytochemistry experiments show that transgene expression is targeted to GH-expressing somatotroph cells. The transgene is five-fold more highly expressed in males than females, and there is an increase in transgene expression leading up to the onset of puberty. The 1.6kb promoter was further examined in cell culture experiments, which revealed that the promoter is selectively activated in pituitary cells and that promoter-reporter expression in non-pituitary cells can be enhanced by the pituitary-specific transcription factor Pit-1. Electrophoretic mobility shift assays identified ten short regions that specifically bind Pit-1 with highly variable relative affinities. The highest affinity site was previously identified and is required for Pit-1 activation of the promoter. Four additional sites contribute to Pit-1 regulation of the promoter and are important to achieving full activation of the gene. The results show that the 1.6kb promoter is sufficient to direct tissue- and cell-specific expression in vivo and is regulated by Pit-1.