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 ovariectomized 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.