In vitro effect of dopastatins on hormone secretion in adrenal tumors
Claudia Pivonello, Tiziana Napolitano, Monica De Leo, Alessia Cozzolino, Pasquale Vitale, Gaetano Lombardi, Annamaria Colao & Rosario Pivonello
Somatostatin (SSTRs) and dopamine (DRs) receptors are expressed in adrenal tumors. It has been demonstrated in pituitary and neuroendocrine tumors that somatostatin-dopamine chimeric molecules, namely dopastatins, which bind both somatostatin (SST2 and/or SST5) and dopamine (D2) receptors, exert a more potent action compared with the single receptor agonists in experimental settings. The aims of this study were to evaluate the expression of DRs and SSTRs, and the effects of dopastatins on hormone secretion in two aldosterone-secreting adenomas, two cortisol-secreting adenomas, as well as in two different adrenocortical carcinoma cell lines (H295R and Hac-15).
The expression of SSTRs and DRs was detected by RT-PCR. Hormone secretion was evaluated by measuring cortisol and aldosterone, before and after the administration of Lanreotide, Cabergoline, BIM 23A765, BIM 23A387 and BIM 23A370 in concentrations ranging from 10−12 to 10−7 M, using a chemiluminescent immunoenzimatic assay.
At RT-PCR, D1 and D5 together with SST1, SST2 and SST5 were expressed in one case of aldosterone-secreting adenoma whereas D2 and D4, together with SST1, SST2 and SST5 were expressed in the other case. Both cortisol-secreting adenomas expressed different SSTRs, together with D1 and D2 in one case and D1, D2 and D4 in the other case. H295R and Hac-15 cell lines showed the same receptor profile expressing D2 and D4 receptors and all SSTRs. In aldosterone and cortisol-secreting adenomas, lanreotide and cabergoline decreased aldosterone and cortisol secretion whereas dopastatins induced a higher inhibition of hormone secretion. A decrease of aldosterone and/or cortisol secretion by both lanreotide and cabergoline, and more potently by dopastatins were found respectively in the H295R and Hac-15 cell lines.
The results of the current study demonstrated that dopastatins are able to modulate aldosterone and cortisol secretion in adrenal tumors, so that they might be potentially useful in the management of adrenal tumors.