Background: Somatostatin (SRIF) is a widely distributed peptide with effects on virtually all endocrine/exocrine secretions and cell proliferation in normal and tumor tissues. In a previous study, we demonstrated specific somatostatin receptor subtype (sst1–5) expression profiles in various adrenal tumors using RT-PCR. In this study, we investigated the effects of SRIF, octreotide (Oct) and the new multi-receptor ligand SOM230 (SOM) on sst expression in primary cell cultures of normal adrenal gland and various adrenal tumors.
Methods: Tissue from 2 normal adrenal glands, 2 aldosterone-producing adenomas (APA), 1 cortisol-producing adenoma (CPA), and 5 pheochromocytomas (PHEO) was obtained following minimally invasive surgery. Single-cell suspensions were prepared by enzymatic dissociation with collagenase. Cells were cultured in serum-free medium and incubated for 48h with and without test hormones. RNA was isolated, and sst mRNA expression levels were investigated using real-time RT-PCR.
Results: SRIF had no significant effect on sst expression. Oct demonstrated significant stimulatory effect (p<0.05) on sst3 expression. Furthermore, in the majority of primary cell cultures, expression of sst4 and sst5 was reduced. A correlation between sst5 expression and Oct induced inhibition of sst4 expression was found (r=-0.85, p<0.01). SOM demonstrated significant inhibitory effect (p<0.05) on sst1 expression. In the majority of tumors, expression of sst2 and sst4 was also inhibited. Correlations were found between expression of sst1 (r=-0.712, p<0.05), sst3 (r=-0.65, p<0.05), and the SOM induced inhibition of sst1 expression, and between sst1 expression and the SOM induced inhibition of sst2 expression (r=-0.86, p<0.05).
Conclusions: The regulatory effects of somatostatin analogues on expression of somatostatin receptors could influence their therapeutic efficacy.
