Prolonged treatment of patients with pituitary prolactinomas with bromocriptine may increase the consistency of the tumor thereby making selective extirpation more difficult. We made quantitative determinations of the amount of perivascular fibrous tissue in prolactinomas on random electron micrographs, comparing a group of 21 patients treated with bromocriptine for periods longer than 3 months and a control group of 21 patients who did not receive bromocriptine. Statistical analysis of the data showed a significant increase of perivascular fibrous tissue in the treated group (P less than 0.002). We suspect that this fibrosis is a consequence of the rapid shrinkage of prolactinoma cells caused by bromocriptine. Presumably, this cell shrinkage causes enlargement of the extracellular and perivascular spaces which are filled by the deposition of collagen, producing a more dense consistency of the adenoma.

The morphometric analysis of the size of adenomatous prolactin cells shows that bromocriptine-induced cell shrinkage halts if treatment with the drug is discontinued for more than 2 days. Different cell components (nucleus, cytoplasm, nucleolus) do not react to treatment to the same extent.

Adenomatous prolactin cells lose 39% of their cytoplasm volume within 7 days after the beginning of bromocriptine treatment. A simultaneous reduction of the rough-surfaced endoplasmic reticulum and the Golgi apparatus occurs. Their membranes are removed by rapid transport along the secretory pathway to the cell surface and to lysosomal destruction.

Electron microscopic morphometric evaluation of the effects of bromocriptine on human prolactinomas during and after short-term parenteral (7 days) and long-term peroral (4-6 weeks) treatment showed that a reduction in size of prolactinoma cells occurs within a few days (half-time to maximum shrinkage, 2.2 days). The number of secretory granules discharged into the intercellular space increased after short-term treatment by a factor of three but the total volume of stored secretory granules did not change significantly. The total volume of cellular lysosomes, both primary and secondary, decreased significantly to about one-half of the pretreatment value. The amount of stored lipoids, end-products of lysosomal activity, decreased in specimens treated for 7 days, but returned to pretreatment levels in specimens treated for 4-6 weeks, suggesting that lysosomal material is discharged from the cells together with the secretory material.

The elevated gingival tissue expression and gingival crevicular fluid levels of L-plastin in both forms of periodontitis may denote the localized involvement of this novel molecule in the pathogenesis of the disease.