Estrogen-induced hyperplasia and neoplasia in the rat anterior pituitary gland. An immunohistochemical study.

Diethylstilbestrol (DES) treatment of weanling F344 female rats resulted in enlarged pituitary glands and diffuse pituitary prolactin (PRL) cell hyperplasia in all animals after 9 and 12 weeks of treatment. Serum PRL was significantly greater than in control rats (P less than 0.001). Immunohistochemical studies showed that most of the pituitary gland cells consisted of PRL cells. Ultrastructural studies showed increased numbers of PRL cells with hyperplasia of the rough endoplasmic reticulum and decreased numbers of secretory granules. There was a decrease in the relative number of growth hormone (GH) and other cell types in the anterior pituitary. Pituitary tumors and normal pituitary glands were dissociated with trypsin and maintained in culture for 3 weeks. The numbers of PRL and GH cells decreased with time in both groups, and there was an increase in the number of fibroblasts. Staining of the culture cells with neuron-specific enolase showed that the anterior pituitary cells were positive for this enzyme, while the fibroblastic cells were negative. When dissociated pituitary cells were cultured in the presence of 10(-9) M DES for 7 days, there was a 42% increase in the number of immunoreactive PRL cells. These results indicate that DES-treated rats provide an excellent model for study of the in vivo and in vitro regulation of pituitary hyperplasia and neoplasia.