This study was performed to evaluate the effects of thyroid-stimulating hormone (TSH) on phosphatidylinositol-4-phosphate 5-kinase type II gamma (PIPKII gamma) gene expression in the thyrocytes of FRTL-5 cells. Although PIPKII gamma mRNA was expressed constantly in the absence of added TSH, its expression increased remark ably in the presence of 10(-9) M TSH. This increase started within 6 h of the addition of TSH, and reached a maximum at 8 h. The mRNA expression properties of PIPKII gamma in the cells were identified using inhibitors. Actinomycin D blocked PIPKII gamma transcription strongly, while cycloheximide did not. In an experiment using 5,6-dichlo-1-beta -D-ribofuranosyl-benzimidaxole, the half-life of PIPKII gamma mRNA was approximately Gh in the presence or absence of TSH, and it was not affected by the stability of the PIPKII gamma mRNA. The effects of TSH on PIPKII gamma gene expression were specific, and other growth factors examined (transferrin, insulin and hpdro-cortisone) did not alter its expression. It is possible that the mechanism of PIPKII gamma gene expression is involved in the permissive effect of the TSH-cAMP cascade proper. Our results indicate, for the first time, that the expression of PIPKII gamma is regulated transcriptionally by TSH in thyrocytes.