Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hofland, L.J. et al.

Hofland, van der Hoek, Feelders, van Aken, van Koetsveld, Waaijers, Sprij-Mooij, Bruns, Weckbecker, de Herder, Beckers, Lamberts,

The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5.

OBJECTIVE: Currently, there is no effective medical treatment for patients with pituitary-dependent Cushing's disease. A novel somatostatin ( SS) analogue, named SOM230, with high binding affinity to SS receptor subtypes sst(1), sst(2), sst(3) and sst(5) was recently introduced. We compared the in vitro effects of the sst(2)-preferring SS analogue octreotide (OCT) and the multi-ligand SOM230 on ACTH release by human and mouse corticotroph tumour cells. METHODS: By quantitative RT-PCR the sst subtype expression level was determined in human corticotroph adenomas. In vitro, the inhibitory effect of OCT and SOM230 on ACTH release by dispersed human corticotroph adenoma cells and mouse AtT20 corticotroph adenoma cells was determined. In addition, the influence of dexamethasone on the responsiveness to OCT and SOM230 was studied. RESULTS: Corticotroph adenomas expressed predominantly sst(5) mRNA (six out of six adenomas), whereas sst(2) mRNA expression was detected at significantly lower levels. In a 72 h incubation with 10 nmol/l SOM230, ACTH release was inhibited in three out of five cultures (range -30 to -40%). Ten nmol/l OCT slightly inhibited ACTH release in only one of five cultures (- 28%). In AtT20 cells, expressing sst(2), sst(3) and sst(5), SOM230 inhibited ACTH secretion with high potency (IC(50) 0.2 nmol/l). Dexamethasone (10 nmol/l) pre-treatment did not influence the sensitivity of the cells to the inhibitory effect of SOM230, suggesting that sst(5) is relatively resistant to negative control by glucocorticoids. CONCLUSIONS: The selective expression of sst(5) receptors in corticotroph adenomas and the preferential inhibition of ACTH release by human corticotroph adenoma cells by SOM230 in vitro, suggest that SOM230 may have potential in the treatment of patients with pituitary-dependent Cushing's disease.[1]

References

The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. Hofland, L.J., van der Hoek, J., Feelders, R., van Aken, M.O., van Koetsveld, P.M., Waaijers, M., Sprij-Mooij, D., Bruns, C., Weckbecker, G., de Herder, W.W., Beckers, A., Lamberts, S.W. Eur. J. Endocrinol. (2005) [Pubmed]

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