A Comparison of Estrogen Effects on Uterine and Pituitary Growth and Prolactin Synthesis in F344 and Holtzman Rats*

Abstract

The pituitary response to chronic estrogen treatment was studied in two strains of rats, the Fischer 344 (F344) and the Holtzman. Silastic tubing implants containing diethylstilbestrol (DES) were placed in weanling animals. Uterine and pituitary growth and protein synthesis were monitored over an 8-week period. The incorporation of [3H]leucine into PRL and GH was measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both F344 and Holtzman strains respond to chronic DES with an increase in PRL synthesis. PRL synthesis is 7% of the total protein synthesis in ovariectomized female controls of both strains and increases to 40–50% in 8-week DEStreated F344 rats and to 35–45% in Holtzman rats. The uterine growth responses were similar in both strains and reached a plateau after approximately 2 weeks. Despite their similarity in PRL synthesis and uterine growth, these two strains differ dramatically in their pituitary growth response to DES. In the F344 strain, pituitaries from treated animals are significantly larger than control pituitaries after 2 weeks and are 6–10 times their normal size by 8 weeks. Holtzman pituitaries do not show a significant increase in size over controls during a treatment period as long as 12 weeks. The growth response in the F344 strain is dose dependent, with implants containing 2.5 mg DES giving a maximal response. In Holtzman rats, implants containing as much as 50 mg DES do not cause a growth response. Withdrawal of the DES stimulus in F344 rats results in a decrease in size and vascularity of the pituitary tumors. The cessation of tumor growth is not accompanied by a decrease in the percentage of PRL synthesis, although total synthesis decreases in proportion to the size of the gland. Transplants of F344 and Holtzman pituitaries to the kidney capsule of DES-treated F1 hybrid recipient animals results in growth of the F344 but not the Holtzman grafts, suggesting that the strain difference lies directly at the level of the pituitary.