A human pituitary tumor-derived folliculostellate cell line

Pituitary cells have been used for the study of hormone synthesis, secretio n, and regulation. However, the lack of human cell lines of pituitary origi n has made such studies in humans very difficult. Activin, a member of the transforming growth factor-beta cytokine family, is secreted by the pituita ry and serves, in addition to regulating hormone biosynthesis, as a regulat or of cell growth and differentiation. In the human pituitary, folliculo-st ellate cells secrete an activin-binding and -neutralizing protein, follista tin. However, the role of these cells in the autocrine/paracrine regulatory mechanisms of activin is poorly understood. We describe a human pituitary- derived folliculostellate cell line, designated PDFS, that was developed sp ontaneously from a clinically nonfunctioning pituitary macroadenoma. PDFS c ells showed an epithelial-like morphology with long cytoplasmic processes. Electron microscopy revealed frequent intercellular junctions, including de smosomes, and cytogenetic analysis showed clonal characteristics with chrom osomal abnormalities. These cells express vimentin and the nervous tissue-s pecific 5-100 protein, specific markers of folliculostellate cells in the a nterior pituitary, but no secretory pituitary cell markers. PDFS cells form ed large colonies in an anchorage-independent transformation assay. They ex press follistatin and activin A and have an intact activin intracellular si gnaling pathway as determined by reporter assays. Therefore, this human cel l line provides a useful model for studying the regulation of cell growth a nd cytokine production by factors endogenously produced in pituitary follic ulostellate cells.