title: Abnormal transduction of dopamine signal in human nonfunctioning pituitary adenomas.
abstract: 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.
authors.affiliation: Istituto di Scienze Endocrine, Ospedale Maggiore IRCCS, Università di Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lania
authors.forename: F
authors.initials: F
authors.lastname: Reza-Elahi
authors.forename: P
authors.initials: P
authors.lastname: Gil-del-Alamo
authors.forename: K
authors.initials: K
authors.lastname: Saccomanno
authors.forename: S
authors.initials: S
authors.lastname: Mantovani
authors.forename: A
authors.initials: A
authors.lastname: Spada
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010911:Pituitary Neoplasms / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000262:Adenylyl Cyclases; D002118:Calcium; D004298:Dopamine