Ultrastructural localization of prolactin in estrogen-induced prolactinoma of the rat pituitary. Experimental models for the human prolactinomas and the effects of bromocriptine.

In order to establish the experimental model for human prolactinomas and its bromocriptine treatment, estrogen-induced prolactinoma was produced in the female Wistar rats, in which daily bromocriptine treatment was given for a week, 3 days or 1 day (24 hours). The prolactinoma was produced by giving 5 mg estrogen depot every four weeks. The rats were killed at 4, 12, 20, and 24 weeks after the initial injection of the estrogen. By immunoelectron microscopy, in the estrogen induced prolactinoma, PRL was localized in well developed lamellar or whorling rough endoplasmic reticulum (RER) and Golgi saccules. In the rats treated with bromocriptine for a week, the serum PRL levels were lowered and the atrophied cytoplasm was filled with secretory granules containing PRL. These data were comparable to those of the human prolactinomas and the present experiment will serve as an animal model for studying the morphofunctional changes of human prolactinomas induced by bromocriptine treatment. The experiment with bromocriptine treatment for 24 hours supported the proposed mechanism that bromocriptine evokes inhibition of exocytosis followed by continuous granule formation in Golgi complexes and subsequently lowers synthesis of PRL.