BIOCHEMICAL PARAMETERS IN THE ANTERIOR-PITUITARY DURING THE COURSE OFTUMORIGENESIS INDUCED BY DIETHYLSTILBESTROL TREATMENT

Treatment of F-344 rats with diethylstilbestrol (DES) for 1-2 months i nduces a prolactin (PRL)-secreting pituitary adenoma. After 8 weeks of DES treatment, we have shown that the ratio of regulatory subunits of the cAMP-dependent protein kinase (RI/RII) increased in the tumors. P resently we report the variations in RI/RII ratio, pituitary weight, D NA content, serum PRL, nuclear estrogen receptor (E(2)R) and of ornith ine decarboxylase (ODC) activity from the time of DES pellet implantat ion until 8 weeks. Pituitary weight, DNA content and serum PRL rose si gnificantly at 4 weeks with a maximum at 6-8 weeks, and significantly correlated with each other. E(2)R and ODC activity increased from week 1 onwards, with a maximum at 2 weeks and decreased at 8 weeks. Both v ariables showed a positive correlation but neither E(2)R nor ODC activ ity correlated with pituitary weight, DNA or serum PRL. Values for RI remained stable with time, but RII decreased progressively. The RI/RII ratio was maintained around unity between 1-4 weeks, increasing to 1. 6-2 thereafter. This ratio positively correlated with pituitary weight and DNA. It is suggested that during tumor induction by estrogen in a sensitive strain of rats, growth signals with different time-courses become activated. Increases in pituitary weight and DNA content, indic ators of mammotroph hypertrophy and hyperplasia, were preceeded by ear ly rises in E(2)R and ODC activity. Increases in the RI/RII ratio acco mpanied the adenomatous change, suggesting their role in cell transfor mation after 6 weeks of estrogen exposure.