SOME CHANGES OF RECEPTOR AND POSTRECEPTOR SIGNAL-TRANSDUCTION REGULATED BY SOMATOSTATIN IN PITUITARY HGH-SECRETING ADENOMAS

Objective To investigate the disturbance in the function of SRIF recep tor, Gi protein and Ca2+ channel in hGH adenoma cells and to evaluate their significance in the pathogenesis of pituitary hGH adenomas. Meth ods All 25 patients with pituitary hGH adenoma who were involved in th is study had typical acromegalic menifestation and high fasting serum hGH levels of >5.0 mu g/L which were not suppressed to <3.0 mu g/L by oral glucose tolerence test. The pituitary hGH adenoma tissue obtained from transphenoidal operation was digested by collagenase and the dis persed adenoma cells were cultured in the monolayer. The effects of oc treotide (SMS), a long-acting agonist of somatostatin, on hGH secretio n and intracellular cAMP level were observed and the influences of per tussis toxin (PT), an inhibitor of Gi protein, and Ca2+ ionophore A231 87 or KCl on the inhibitory action of octreotide on hGH secretion were also investigated in the cultured pituitary hGH adenoma cells. Result s A total of 16.0% (4/25) of cultured pituitary hGH adenomas did not r espond to octreotide (100 nmol). The inhibitory effect of octreotide o n hGH secretion was not blocked by PT (50 ng/ml) and A23187 (10 mu mol ) or KCl (22.5 nmol) in 31.6% (6/19) and 35% (7/20) of hGH adenomas, r espectively. The effects of octreotide on hGH secretion and intracellu lar cAMP levels mere studied in 10 cultured hGH adenomas. Octreotide s uppressed both hGH secretion and cAMP levels in 5 cases: inhibited onl y hGH secretion or the cAMP level in 3 cases and 1 case respectively: and affected neither hGH secretion nor cAMP level in the last case. Co nclusion There were abnormalities in the SRIF receptor and/or postrece ptor signal transduction in 16.0% of hGH adenomas which did not respon d to octreotide. The defects in Gi and/or Ca2+ channels were found in 52.4% (11/21) of hGH adenomas which had responded to octreotide. These defects might induce diminution of the inhibitory action of SRIF on h GH secretion and might be the causes of hypersecretion in some pituita ry hGH adenomas.