Differential transduction of dopamine signal in different subtypes of human growth hormone-secreting adenomas.
This article reports the effect of dopamine (DA) on adenylyl cyclase (AC) activity and intracellular free calcium concentration ([Ca2+]i) in 20 GH-secreting pituitary adenomas exclusively composed of somatotrophs (GH-omas) and 3 tumors largely constituted by mammosomatotrophs (MS-omas). DA (between 10 nmol/L and 100 mumol/L) did not reduce AC activity in any GH-omas, whereas the amine caused a significant inhibition in membranes from all MS-omas. The effect was detectable at DA concentrations higher than 0.1 mumol/L, and maximal inhibition (ranging from 24-30%) was reached at 10 mumol/L. The ergot derivative CH 29717 and l-sulpiride demonstrated potent agonist and antagonist activities, respectively. Somatostatin reduced AC activity in all tumors; the percent inhibition values (between 17-34%) were similar in GH-omas and MS-omas. In both GH-omas and MS-omas, DA (1 mumol/L) caused a significant [Ca2+]i reduction (between 17-44%) that was essentially due to the block of Ca2+ influx from the extracellular spaces. The receptors involved in this effect showed the pharmacological properties of D2 receptors. In conclusion, the DA effect in tumoral somatotrophs is defective; DA fails to exert an inhibitory action on AC activity. In mammosomatotrophs, the typical D2 receptor-effector coupling is retained, resulting in decreased AC activity in these cells.
Spada
A
A
Institute of Endocrine Sciences, Maggiore Hospital IRCCS, Milan, Italy.
Bassetti
M
M
Reza-Elahi
F
F
Arosio
M
M
Gil-Del-Alamo
P
P
Vallar
L
L
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D000262:Adenylyl Cyclases / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D011954:Receptors, Dopamine / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
D011954:Receptors, Dopamine; D013004:Somatostatin; D013469:Sulpiride; D013006:Growth Hormone; D000262:Adenylyl Cyclases; D002118:Calcium; D004298:Dopamine