Effects of Somatostatin Analogs on Catecholamine Biosynthesis Regulated by Corticosteroids and Bone Morphogenetic Proteins in Rat Pheochromocytoma Cells

Regulatory roles of SSAs in catecholamine synthesis have not been elucidated. To clarify the actions of SSAs on catecholamine biosynthesis, we investigated the mutual interactions among SSAs including octreotide and pasireotide, steroids and BMPs using rat pheochromocytoma PC12 cells. Treatment with octreotide and pasireotide (10 nM to 10 μM) had no significant effect on mRNA levels of Th, DOPA decarboxylase and dopamine-β-hydroxylase in PC12 cells. Regarding the interaction with steroids, treatments with SSAs also had no effect on dexamethasone- or aldosterone-induced Th mRNA expression, while pasireotide reduced mRNA expression of the GR. As for the interaction with BMP-4, which can suppress Th mRNA expression by PC12 cells, SSAs did not affect Th expression reduced by BMP-4 and Id1 or Smad1/5/9 activation induced by BMP-4. However, BMP-4 treatment up-regulated MR expression, while treatment with noggin, which neutralizes endogenous BMPs, downregulated MR expression, and the presence of noggin also attenuated aldosterone-induced Th expression, suggesting that endogenous BMPs act to enhance MR activity. Moreover, BMP-4 treatment suppressed the expression of somatostatin receptors including Sstr2 and Sstr5 in PC12 cells, while treatment with noggin up-regulated the expression of Sstr2 and Sstr5, suggesting that BMPs play a desensitizing role in SSA actions. Collectively, the results revealed that SSAs have no direct effect on catecholamine synthesis; however, adrenomedullar BMPs could be modulators for the responsiveness to MR and SSTRs.