Related Experiment Videos
Differential transduction of dopamine signal in different subtypes of human growth hormone-secreting adenomas
A Spada1, M Bassetti, F Reza-Elahi
1Institute of Endocrine Sciences, Maggiore Hospital IRCCS, Milan, Italy.
Abstract:
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.
Insights
Dopamine (DA) fails to inhibit adenylyl cyclase (AC) in GH-secreting pituitary tumors (GH-omas) but reduces AC activity in mammosomatotroph (MS-omas) tumors, indicating a defect in DA signaling in GH-omas.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Dopamine (DA) plays a role in regulating pituitary hormone secretion.
- Pituitary adenomas, particularly GH-secreting tumors, are a significant clinical concern.
Purpose of the Study:
- To investigate the effect of dopamine on adenylyl cyclase (AC) activity and intracellular calcium ([Ca2+]i) in GH-secreting pituitary adenomas.
- To characterize the dopamine receptor subtypes involved in these effects.
Main Methods:
- Assessed AC activity and [Ca2+]i in GH-omas and mammosomatotroph (MS-omas) tumor samples.
- Utilized dopamine, dopamine agonists (CH 29717), and antagonists (l-sulpiride) to study receptor pharmacology.
- Investigated the impact of somatostatin on AC activity.
Main Results:
- Dopamine did not inhibit AC activity in GH-omas but significantly inhibited it in MS-omas.
- Dopamine reduced [Ca2+]i in both tumor types by blocking extracellular calcium influx, mediated by D2 receptors.
- Somatostatin inhibited AC activity similarly in both GH-omas and MS-omas.
Conclusions:
- Dopamine signaling is defective in GH-secreting pituitary adenomas (GH-omas), specifically its inhibitory effect on AC activity.
- Mammosomatotroph (MS-omas) tumors retain functional D2 receptor-mediated inhibition of AC activity.
- These findings highlight differential dopamine responsiveness in pituitary adenoma subtypes.