EFFECT OF BROMOCRIPTINE AND SMS-201-995 ON GROWTH OF HUMAN SOMATOTROPIC AND NONFUNCTIONING PITUITARY-ADENOMA CELLS IN-VITRO

The effect of the dopamine agonist bromocriptine and the somatostatin analog SMS 201-995 on growth of 12 human somatotrophic and 13 non-func tioning adenoma cell cultures was investigated. When adenoma cells wer e maintained in medium supplemented with 5% fetal calf serum, cell cou nts of 10 of 12 somatotrophic cultures increased to 145 +/- 6 and 171 +/- 9% (mean +/- SD) and in 12 of 13 nonfunctioning cell cultures up t o 125 +/- 12 and 217 +/- 115% after 3 days of incubation. In most case s bromocriptine and SMS 201-995 dose dependently (1 nmol/l to 10 mu mo l/l) inhibited adenoma cell growth but there was only (1, 10 mu mol/l) a significant inhibitory effect at high doses of both drugs. A 1 mu m ol/l concentration of bromocriptine decreased cell counts of 5 of 12 s omatotrophic cell cultures (range 84 +/- 3 to 76 +/- 6% vs control = 1 00%) and in 5 of 13 non-functioning cell cultures (range 85 +/- 4 to 7 1 +/- 7%). A 10 mu mol/l concentration of bromocriptine decreased cell counts in all 12 somatotrophic (range 87 +/- 1 to 61 +/- 8%) and in 1 2 of 13 non-functioning adenoma cultures (range 87 +/- 6 to 57 +/- 3%) . Bromocriptine specifically inhibited growth because its effect could be reversed by the dopamine D-2-receptor antagonist haloperidol. Both 1 and 10 mu mol/l SMS 201-995 significantly decreased cell counts in three of six somatotrophic (87 +/- 3 to 38 +/- 3%) cell cultures. In t wo of five cases growth of non-functioning adenoma cultures was suppre ssed by 1 mu mol/l SMS 201-995, and in four of five cases by 10 mu mol /l (86 +/- 3 to 74 +/- 4%). The growth inhibitory effect of bath; brom ocriptine and SMS 201-995 was not just due to an effect on growth of f ibroblasts contaminating the adenoma cell cultures, because it could b e observed also when adenoma cells were maintained in a D-valine-suppl emented medium that suppresses fibroblast growth. In summary, both bro mocriptine and SMS 201-995 at high doses were able to inhibit cell gro wth of cultured somatotrophic and non-functioning adenomas in vitro. H owever, the mechanism of this inhibitory effect is not yet well unders tood.