Strain Difference in Regulation of Pituitary Tumor Transforming Gene (PTTG) in Estrogen–induced Pituitary Tumorigenesis in Rats

Recently a novel oncogene, PTTG (pituitary tumor transforming gene) was isolated from a rat pituitary tumor cell line whose expression is apparently correlated with pituitary tumorigenesis. In the rat, estradiol (E(2)) is known to induce anterior pituitary hyperplasia. The effects of E(2), however, vary greatly among rat strains. Therefore we examined the expression of PTTG and its regulation by E(2) in F344, Wistar, Brown–Norway and Donryu rats. Four–week–old females were ovariecto–mized and a pellet containing 10 mg of E(2) was given s.c. Total RNA was isolated from the pituitary gland and PTTG mRNA was measured with a competitive RT–PCR technique. The F344 strain was the most susceptible to E(2) induction of pituitary tumorigenesis, followed by Wistar and Brown–Norway, while no increase in pituitary weight was noted in Donryu rats. PTTG mRNA in the gland was induced by E(2) within 48–72 h in F344 and Wistar, but not in Brown–Norway or Donryu strains. These data suggest that PTTG expression may at least in part be responsible for strain differences in E(2)–induced pituitary tumorigenesis