Abnormal transduction of dopamine signal in human nonfunctioning pituitary adenomas

It is well established that dopamine (DA) plays an important role in inhibiting anterior pituitary function. DA receptors present in the pituitary show the pharmacological and biochemical characteristics of the D2 receptor; in fact, they are coupled to the inhibition of both adenylyl cyclase (AC) activity and the reduction of cytosolic free Ca2+ levels ([Ca2+]i) suggesting the involvement of different G-proteins. While the DA receptors present in human PRL-omas display these characteristics, no information is available on the coupling mechanism(s) of DA receptors expressed in nonfunctioning pituitary adenomas (NF-PA). In the present study, the effect of DA on AC activity and [Ca2+]i was investigated in 8 NFPAs surgically removed by the transphenoidal route. DA, at concentrations between 0.01 and 10 mumol/l, had no effect on cAMP formation in any tumor (from 27.6 +/- 11.9 to 27.9 +/- 11.0 pmol/mg prot/min; NS). By contrast, DA was effective in reducing [Ca2+]i levels either in resting conditions or after TRH stimulation in 5 out of 8 tumors, suggesting that NFPA express DA receptors with a defective transduction mechanism. As in these tumors SRIH caused the expected inhibition of both AC activity (from 31.4 +/- 9.3 to 24.4 +/- 11.0 pmol/mg prot/min; p < 0.005) and [Ca2+]i levels, it is likely that the lack of DA action on AC activity may be due to functional/structural properties of DA receptors expressed in NFPA, instead of a defect at the level of Gi proteins. In conclusion, these data indicate that DA receptors expressed in NFPA show a defective transduction mechanism, leading to a partial inhibitory response.