The role of GRH mediated AC-cAMP system in the pathogenesis of human pituitary GH-secreting adenomas.
OBJECTIVE
To investigate the role of AC-cAMP system in the transmission of the action of the growth hormone releasing hormone (GRH) on growth hormone (GH) release in pituitary GH-secreting adenomas.


METHODS
The effects of GRH (10(-7) mol/L) on intracellular cAMP levels and GH release and the effects of AC-cAMP stimulators, cholera toxin (Ct, 50 micrograms/L), forskolin (10(-5) ml/L) and db-cAMP (10(-3) mol/L) on GH secretion were studied in cultured cells of 21 GH-secreting adenomas obtained from operation for acromegalic patients.


RESULTS
GRH and Ct failed to stimulate GH secretion in 61.9% (13/21 cases) and 57.1% (12/21 cases) pituitary GH adenoma cell cultures respectively. Forskolin stimulated GH release in 88.9% (8/9 cases), while db-cAMP induced GH secretion in all cases tested (5/5 cases). The intracellular cAMP levels were elevated by GRH in the 4 out of 9 cases of tumor cell cultures, but not in the other 5 cases. According to the GH secretory responses to GRH and Ct, the 21 GH tumors were divided into 4 groups. In group A and B, GRH can stimulate GH release, but Ct has stimulative role only in group A. In group C and D, GRH fails to stimulate GH secretion. However group A can respond to Ct, but group D has no response.


CONCLUSIONS
The GH hypersecretion in most acromegalic patients is mainly due to the defects of pituitary adenoma cells, especially the abnormalities of GRH receptor and/or stimulative guanosine protein.
Shi
Y
Y
Department of Endocrinology, Peking Union Medical College Hospital, Beijing Union Medical University, Chinese Academy of Medical Sciences.
Deng
J
J
Yin
J
J
D000239:Adenoma, Acidophil / Q000378:metabolism*; D000238:Adenoma, Chromophobe / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology*; D006801:Humans; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011986:Receptors, Somatotropin; D014407:Tumor Cells, Cultured
D011986:Receptors, Somatotropin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases