Effect of bromocriptine and SMS 201-995 on growth of human somatotrophic and non-functioning 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-functioning adenoma cell cultures was investigated. When adenoma cells were maintained in medium supplemented with 5% fetal calf serum, cell counts of 10 of 12 somatotrophic cultures increased to 145 +/- 6 and 171 +/- 9% (mean +/- SD) and in 12 of 13 non-functioning cell cultures up to 125 +/- 12 and 217 +/- 15% after 3 days of incubation. In most cases bromocriptine and SMS 201-995 dose dependently (1 nmol/l to 10 mumol/l) inhibited adenoma cell growth but there was only (1, 10 mumol/l) a significant inhibitory effect at high doses of both drugs. A 1 mumol/l concentration of bromocriptine decreased cell counts of 5 of 12 somatotrophic cell cultures (range 84 +/- 3 to 76 +/- 6% vs control = 100%) and in 5 of 13 non-functioning cell cultures (range 85 +/- 4 to 71 +/- 7%). A 10 mumol/l concentration of bromocriptine decreased cell counts in all 12 somatotrophic (range 87 +/- 1 to 61 +/- 8%) and in 12 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 D2-receptor antagonist haloperidol. Both 1 and 10 mumol/l SMS 201-995 significantly decreased cell counts in three of six somatotrophic (87 +/- 3 to 38 +/- 3%) cell cultures. In two of five cases growth of non-functioning adenoma cultures was suppressed by 1 mumol/l SMS 201-995, and in four of five cases by 10 mumol/l (86 +/- 3 to 74 +/- 4%). The growth inhibitory effect of both bromocriptine and SMS 201-995 was not just due to an effect on growth of fibroblasts contaminating the adenoma cell cultures, because it could be observed also when adenoma cells were maintained in a D-valine-supplemented medium that suppresses fibroblast growth. In summary, both bromocriptine and SMS 201-995 at high doses were able to inhibit cell growth of cultured somatotrophic and non-functioning adenomas in vitro. However, the mechanism of this inhibitory effect is not yet well understood.
Renner
U
U
Max-Planck-Institute of Psychiatry, Munich, Germany.
Mojto
J
J
Lange
M
M
Müller
O A
OA
von Werder
K
K
Stalla
G K
GK
D000236:Adenoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D001971:Bromocriptine / Q000494:pharmacology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D003470:Culture Media; D016895:Culture Media, Serum-Free; D001971:Bromocriptine; D015282:Octreotide