Basic fibroblast growth factor: the neurotrophic factor influencing the ingrowth of neural tissue into the anterior pituitary of alpha-T7 transgenic mice?

alpha-T7 mice are a transgenic line which carries a hybrid transgene composed of the 5' flanking region of the human glycoprotein hormone alpha-subunit gene (1.8 kb) linked to the coding region of the oncogene SV40 T-antigen. Large, hemorrhagic, pituitary tumors form in these mice and contain giant, transformed gonadotropes (immunopositive for T-antigen), in addition to normal-appearing gonadotropes (also immunopositive for T-antigen). An additional feature of these tumors is an abundance of neural tissue proliferating throughout the anterior pituitary, concentrated around the giant gonadotropes, and forming synaptoid contacts upon them. Continued study of these mice has demonstrated that the giant gonadotropes contain immunostainable basic fibroblast growth factor (FGF-2), and apparently release the FGF by focal cellular disruption and/or cytoplasmic blebbing. Normal gonadotropes, in control and transgenic mice, were strongly immunopositive for FGF, and appeared intact. In 8- to 13-month-old transgenic mice most of the giant cells were intact, and were surrounded by well-differentiated neural tissue. These giant cells were lightly immunopositive for FGF. Disrupted, giant gonadotropes were more frequent in 2- to 7-month-old transgenic mice, and also were surrounded by well-differentiated neural tissue with many synaptoid contacts. These cells generally were moderately immunopositive for FGF. In neonatal mice, 1-8 days old, precursors of the giant, transformed gonadotropes were identified, primarily, but not exclusively, near the periphery of the anterior pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)