Increased exocytosis of secretory granules in contrast to reduced serum hormone levels in pituitary adenomas of humans and rats treated with dopamine agonist.

Abstract

The release of secretory granules outside the cells increased in frequency, in inverse proportion to the marked decrease in serum prolactin (PRL) levels in human prolactin-secreting adenomas (PRLomas) treated with bromocriptine (CB), a dopamine agonist. Rat pituitary adenomas induced by diethylstilbestrol also showed an increase in exocytosis of the granules despite a reduction in serum PRL levels after CB treatment. To elucidate this curious phenomenon, which is contrary to current general knowledge that serum hormone levels are sustained by the exocytosis of the secretory granules, we combined morphometric analysis with analyses using a cell fractionation technique and immunocytochemistry. The results indicated that the proteins in secretory granules consisted of 90% nonhormonal proteins and 10% PRL. CB treatment did not change the levels of the former, while the levels of the latter were markedly reduced. Immunocytochemistry, using a protein-A gold method, revealed that the secretory granules in rats treated with CB contained fewer PRL molecules than the controls. Serum PRL elevation caused by the exocytoses, estimated by counting the exocytotic granules, were markedly lower (less than 10%) in CB-treated rats than in the controls. It was suggested that, after CB treatment, the composition of secretory granules altered, or that nonhormonal constituents in the granules disintegrated more slowly, and that the granules became detectable at the site of release for a longer period. Consequently, although granules that appear ultrastructurally similar to those in untreated adenomas are observed to be more frequently released in treated adenomas, it seems that they no longer contribute to raising the serum PRL levels.