Aspects of medical therapy of neuroendocrine disorders.

The effects of long term in vitro exposure witil octreotide of human GH secreting pituitary adenoma cells were investigated on GH release, intracellular GH concentrations, and GH mRNA levels. Incubation of tile adenoma cells for 4 days witil 10nM octreotide induced a dose-dependent inhibition of GH release, while in parallel an increase (maximal increase varying between 24 and 517%) in the intracellular GH levels was observed in 6 of 7 adenomas. In addition bromocriptine, when effective in inhibiting GH release by tile adenomas, also induced an increase in intracellular GH levels. Even after tbree weeks of exposure to 10nM octreotide in vitrO tilere was a statistically significant increase in intracellular GH levels (variation between 91 and 923% increase). Witildrawal of octreotide after 6 days of incubation resulted in a lowering of intracellular GH levels to control values, showing tilat tile octreotideinduced increase in intracellular GH is reversible. In a 96 h incubation witil 10nM octreotide GH mRNA levels were increased in 2, and slightly decreased in 1 of tile 3 adenomas tested. This effect was time-dependent in that there was no significant effect of 10nM octreotide on GH mRNA levels in a 24 h incubation. We conclude tilat: 1) long-term in vitro exposure of GH-adenoma cells to octreotide causes an increase in intracellular GH levels in the majority of tile adenomas, which is probably due to an increase in GH mRNA levels in the adenoma cells; and 2) tbis considerable increase in intracellular GH levels may be one of tile explanations for tile relatively poor effect of octreotide on tumour shrinkage in patients witil GHsecreting pituitary adenomas.