Cytosuppressive Effect of Bromocriptine on Human Prolactinomas: Stereological Analysis of Ultrastructural Alterations with Special Reference to Secretory Granules1

To ascertain the mechanisms of bromocriptine in lowering serum prolactin (PRL) levels and reducing the cell size of human prolactinomas, Stereological analysis at electron microscope level was performed on six adenomas treated with bromocriptine (10 mg/day for 2 weeks) and four untreated adenomas. The bromocriptine treatment significantly decreased all the major organelles involved in PRL synthesis when expressed in absolute volume per single tumor cell, although it decreased only Golgi apparatus when expressed in relative volume within the cells. Secretory granules, lysosomes, and lipid droplets increased in relative volume but not in absolute volume in bromocriptinetreated adenomas. Consequently, bromocriptine decreased the volume of individual tumor cell to approximately 60% of that of untreated tumor cells. Unexpectedly, exocytosis of secretory granules increased significantly in the bromocriptine-treated ad enomas in spite of a remarkable decrease in serum PRL levels. This appears to be contradictory to the current view that a decrease in serum PRL levels with a concurrent increase in the intracellular PRL levels caused by bromocriptine treatment re sults from the inhibition of exocytosis of secretory granules. The secretory granules of bromocriptine-treated adenomas may con tain a small amount of PRL, as suggested by a culture study reporting degradation of PRL by bromocriptine.