Stimulation by estradiol-17 beta of thymidine kinase activity in the rat uterus

Abstract

The action of estradiol-17 beta (E2) on thymidine kinase (TK) activity was studied in uteri from immature female rats. It was demonstrated that a single injection of E2 highly stimulated the enzyme activity which reached its maximum level 24 h after hormone administration. Physiological amounts of E2 were efficient and changes in TK activity were observed exclusively in uterus and liver. A single injection of Tamoxifen produced the same effect as E2 but repeated administration resulted in the complete inhibition of enzyme activity. Using antibiotics it was demonstrated that E2 induced the synthesis of new enzyme molecules rather than an increase in enzyme activity. This statement was corroborated by the fact that after hormone administration the increase in TK activity was preceded by an increase in RNA-polymerase activity and followed by that in DNA-polymerase alpha activity. Moreover, the separation of TK isoenzymes on DEAE-Sephadex and the use of d-CTP as inhibitor of the adult isozyme suggested that E2 induced the "fetal" form of the enzyme. In addition, it was demonstrated that TK activity in uteri from ovariectomized adult female rats was enhanced by E2 administration, and that the increase was due to the stimulation of the fetal isoenzyme. It was suggested that TK could be used as a marker of the action of estrogens and antiestrogens in target organs.