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The effect of dopamine (DA) on GH release was studied in monolayer cultures obtained from 21 GH-secreting pituitary adenomas. DA at a concentration of 10(-6) M inhibited GH release in 13 adenomas (group 1: inhibition from 27--74%), had no effect in 3 (group II), and elicited a marked stimulation in 5 (group III: stimulation from 62--170%). The adenomas of acromegalic patients which were preoperatively responsive to DNA infusion (4 micrograms/kg . min) al fell into group I, whereas adenomas from patients not responsive to DA in vivo fell into groups II and III. The dose dependency of the effect of DA on GH secretion was studied in groups I and III. In group I adenomas the maximal inhibition was from 32--76% between 10(-7) and 2 x 10(-5) M DA. At high concentrations DA elicited a stimulatory effect. In group III adenomas the maximal stimulation was from 95--310% between 10(-7) and 10(-5) M DA. The dopaminergic ergot derivative CH 29--717 was as potent as DA in inhibiting GH release but, in contrast to DA, was nearly ineffective in stimulating the secretion of the hormone. We hypothesize that the different in vitro responsiveness of GH-secreting pituitary adenomas to DA could be due to the presence of multiple forms of DA receptors.

A morphological study was carried out on eight macroprolactinomas surgically removed from untreated patients and on nine macroprolactinomas removed from patients treated with bromocriptine (Brc; seven from patients treated for 6 weeks and two from patients treated for 1 yr). All treated patients had both serum PRL levels and tumor size (by computed tomographic scan) reduced. The study was carried out using light, immunofluorescence, and electron microscopic techniques and electron microscopic morphometry. By immunofluorescence microscopy, all tumors consisted of cells positive for PRL. In some treated tumors, the fluorescence was more marked than in untreated tumors. By light and electron microscopy and by morphometry, significant reductions in cell size were observed in the adenomas from Brc-treated patients. Both the cytoplasm and the nucleus shrank, but the reduction of the cytoplasm was much greater than that of the nucleus. The shrinkage of the cytoplasm was a consequence of marked involution of the rough endoplasmic reticulum and the Golgi complex in Brc-treated tumors. This effect may be related to inhibition of PRL synthesis by the drug. In some tumors from treated patients, the number of secretory granules was increased. No differences were observed between tumors from patients treated for 6 weeks and those from patients treated for 1 yr. The observed reduction in cell size by Brc could explain, at least in part, the well known size reduction of PRL-secreting adenomas in patients treated with the drug.