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Some changes of receptor and postreceptor signal transduction regulated by somatostatin in pituitary hGH-secreting
Objective:
To investigate the disturbance in the function of SRIF receptor, Gi protein and Ca2+ channel in hGH adenoma cells and to evaluate their significance in the pathogenesis of pituitary hGH adenomas.
Methods:
All 25 patients with pituitary hGH adenoma who were involved in this study had typical acromegalic manifestation and high fasting serum hGH levels of > 5.0 micrograms/L which were not suppressed to < 3.0 micrograms/L by oral glucose tolerance test. The pituitary hGH adenoma tissue obtained from transphenoidal operation was digested by collagenase and the dispersed adenoma cells were cultured in the monolayer. The effects of octreotide (SMS), a long-acting agonist of somatostatin, on hGH secretion and intracellular cAMP level were observed and the influences of pertussis toxin (PT), an inhibitor of Gi protein, and Ca2+ ionophore A23187 or KCl on the inhibitory action of octreotide on hGH secretion were also investigated in the cultured pituitary hGH adenoma cells.
Results:
A total of 16.0% (4/25) of cultured pituitary hGH adenomas did not respond to octreotide (100 nmol). The inhibitory effect of octreotide on hGH secretion was not blocked by PT (50 ng/ml) and A23187 (10 mumol) or KCl (22.5 nmol) in 31.6% (6/19) and 35% (7/20) of hGH adenomas, respectively. The effects of octreotide on hGH secretion and intracellular cAMP levels were studied in 10 cultured hGH adenomas. Octreotide suppressed both hGH secretion and cAMP levels in 5 cases; inhibited only 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.
Conclusion:
There were abnormalities in the SRIF receptor and/or postreceptor signal transduction in 16.0% of hGH adenomas which did not respond 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 hGH secretion and might be the causes of hypersecretion in some pituitary hGH adenomas.