Cell type-specific adenoviral transgene expression in the intact ovine pituitary gland after stereotaxic delivery: An in vivo system for long-term multiple parameter evaluation of human pituitary gene therapy

Ablative therapies for pituitary tumors commonly cause irreversible damage to normal pituitary cells. Toxin gene therapy should therefore ideally be t argeted to specific cell types to avoid collateral cell damage. To evaluate cell-type-specific adenoviral gene transfer in the intact pituitary gland we have used stereotaxic transcranial delivery of recombinant adenoviruses in the sheep with continuous assessment of endocrine function. Adenoviral b eta -galactosidase expression was driven either by the human cytomegaloviru s (hCMV) promoter or the human PRL gene promoter. The hCMV promoter directe d adenoviral beta -galactosidase expression in all pituitary cell types, bu t the PRL promoter restricted this exclusively to lactotropic cells, indica ting that this promoter conferred appropriate cell type specificity in the context of adenoviral transduction in vivo. Serial measurements of plasma h ormones showed no disruption of endocrine function over 7 days after intrap ituitary injection. Ln summary, this work shows cell type-specific expressi on of an adenoviral transgene in the mixed cell population of the intact pi tuitary gland in vivo in a large animal model and indicates that stereotaxi c intrapituitary delivery does not disrupt normal endocrine function.