Somatostatin receptors: from basic science to clinical approach—thyroid

Abstract

Somatostatin and its receptors are expressed in the thyroid gland, but somatostatin analogs which are currently available have provided contradictory results in the diagnosis and treatment of thyroid neoplasia. Somatostatin and its analogs fail to influence follicular thyroid function, whereas their administration in patients with medullary thyroid carcinoma induces a reduction of serum calcitonin concentrations and clinical symptoms, but fails to influence tumour size and patient survival rate. Radiolabelled somatostatin analogs can localise tumours expressing somatostatin receptors, but somatostatin receptor-targeted radiotherapy of thyroid malignancies has provided conflicting and inconclusive results. Our recent results indicate that somatostatin receptor 2 activation by somatostatin receptor 2 agonists inhibits cell proliferation in the human medullary thyroid carcinoma cell line, TT. This effect can be hampered by concurrent somatostatin receptor 5 selective agonist treatment, which fails to influence TT cell proliferation, suggesting an antagonism between somatostatin receptors 5 and 2 agonists in medullary thyroid carcinoma cells. Moreover, somatostatin receptors 2 or 5 agonists fail to inhibit calcitonin secretion and calcitonin gene expression. On the other hand, somatostatin receptor 1 agonists inhibit proliferation, calcitonin secretion and calcitonin gene expression in parafollicular C cells, suggesting that analogs with enhanced somatostatin receptor 1 affinity and selectivity besides having great potentiality as pharmacological tools to control neoplastic growth, may also be used to reduce symptoms in patients with medullary thyroid carcinoma.