Chromosomal changes in rat pituitary and bone marrow induced by long-term estogen administration

Pituitary weight, mitotic index and chromosomes were studied in male rats following a single or repeated dose of estradiol-benzoate for a total period of 210 days. Estrogen-induced pituitary hyperplasy eventually resulted in large pituitary tumors in some animals. The mitotic index increased until day 90, when it diminished, with chromosomes partly replaced by chromatin clusters. Most of the cells of the hyperplastic pituitaries maintained a normal diploid karyotype. However, a limited number of abnormal stem-lines with marker chromosomes appeared at a relatively early stage of the hyperplastic reaction of the pituitary. Later the tumors were characterized by an increase of number of aneuploid cells. In the bone marrow estrogens significantly lowered the mitotic index without any detectable change in chromosomal morphology.