The functional role of somatostatin receptor subtypes in pituitary adenomas

The main subject of the current thesis is the role of somatostatin (SRIF) receptors subtype 2 and 5 in the patho-physiological regulation of GH and ACTH release from human pituitary adenomas. The sst expression pattern in both types of pituitary adenomas is evaluated with respect to the inhibitory effects by SRIF-analogs on hormone secretion from the primary cultured tumor cells. The novel multiligand SOM230, compared with the current clinically available SRIF-analog OCT, is evaluated both for its clinical potential in the medical treatment of acromegaly, as well for in vitro for its potential in the medical treatment in patients with Cushing’s disease. SOM230, together with sst-selective analogs and chimeric molecules, targeting the sst2, sst5 and Dopamine D2 Receptor, are used as tools to retrieve insights with respect to the functional interplay between sst2, sst5 and D2R in the regulation of adenylyl cyclase activity as well the susceptibility of sst receptors to undergo ligand-induced adaptation, i.e. tachyphylaxis, of inhibition of adenylyl cyclase activity by SRIF-analogs