The Role Of Second Messenger Systems In The Pathogenesis Of Human Pituitary Growth Hormone (GH)-Secreting Adenomas

The pathogenesis of pituitary adenomas remains unknown at present. The secretion of GH from the somatotrophs of the pituitary is controlled by two hypothalamic peptide hormones, GHRH which stimulates GH release and somatostatin which is a GH relase-inhibiting hormone. GHRH and SRIF act on somatotrophs by binding to the cell surface receptors, thus activating intracellular signals. Both AC-cAMP and Ca²⁺-CaM system have been implicated as intracellular signals in the regulation of GH release by the two hypothalamic hormones. Our previous in vitro investigations had demonstrated that about 2/3 GH secreting pituitary tumors had abnormal or no response to hypothalamic neuroendorcrine hormones GHRH SRIF and TRH, indicating that the dysfunction of receptors and postreceptors of pituitary GH adenoma cells may piay a role in the pathogenesis. In the present experiments we have studied whether the hypersecretion and cell hyperplasia of GH secreting adenoma could be accounted for by alterations of intracellular second signals system . GH- secreting human pituitary adenomas obtainedfrom 21 patients at trans-sphenoidal surgery were studied. First, the effects of AC-cAMP stimulators and inhibitors on the release of GH were tested, we use GHRH, chelora toxin (CT, stimulator of Gs), forskolin...