Effect of somatostatin on adenylate cyclase activity in normal and neoplastic thyroid tissue

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Abstract
Thyroid stimulating hormone (TSH) and other substances increase adenylate cyclase (AC) activity and growth of normal and neoplastic thyroid tissue. Factors that inhibit cAMP may provide targeted therapy to tumors dependent on cAMP for growth. Somatostatin has been reported to inhibit the growth of gastrinomas and carcinoid tumors. We therefore studied the effects of somatostatin on basal, TSH, pertussis toxin, and forskolin stimulated adenylate cyclase activity in normal and neoplastic thyroid tissue from 19 patients. Adenylate cyclase (AC) activity was determined by the conversion of alpha32P-ATP to32P-cAMP in pmoles/mg protein/30 minutes in an 8000 × g particulate fraction rich in thyroid plasma membranes. TSH (300 mU/ml) and forskolin (100 mM) (a diterpine that directly stimulates the catalytic unit of AC) increased AC activity in normal and neoplastic thyroid tissue. The AC stimulation was greater in the neoplasms (p−6M) decreased basal and TSH stimulated AC activity below basal levels in both normal and neoplastic thyroid tissue (including papillary, follicular, and medullary carcinomas). The inhibition of AC by somatostatin was greater in neoplastic tissue (pp−6 M) a entriné une dimunution de l'activité de l'AMPc basale et de celle après stimulation par la TSH des thyroïdes normale et néoplasique (qu'il s'agisse de cancers papillaire, folliculaire ou médullaire). L'inhibition par la somatostatine était plus importante dans le tissu néoplasique (pp−6 M) disminuyó la actividad de AC basal y la estimulada por TSH a niveles inferiores a los valores basales, tanto en el tejido normal como en el tejido neoplásico (incluso carcinomas...