Human pheochromocytomas, but not adrenal medulla, express glucagon-receptor gene and possess an in vitro secretory response to glucagon.
Glucagon-receptor mRNA was detected by reverse transcription-polymerase chain reaction in three human pheochromocytomas, but not in four normal adrenal medullas. Quantitative autoradiography demonstrated the presence of abundant [(125)I-Thyr(10)]glucagon binding sites in pheochromocytomas, which were displaced by both cold glucagon and the glucagon receptor antagonist Des-His(1)[Glu(9)]glucagon amide (GR-A). Adrenal medulla was weakly labeled, and the binding was not displaced by GR-A. Glucagon enhanced epinephrine and norepinephrine release by pheochromocytoma slices, minimal and maximal effective concentrations being 10(-8) M and 10(-6) M. Adrenomedullary slices evidenced a weak catecholamine response only to 10(-5) M glucagon. GR-A abolished the secretory response to glucagon of pheochromocytomas, but not of adrenal medullas. Collectively, these findings indicate that human pheochromocytomas, but not adrenal medulla, express glucagon receptors and possess a marked secretory response to glucagon, thereby providing the rationale to explain the specificity of the glucagon provocative test in the diagnosis of pheochromocytoma.
Albertin
G
G
Department of Human Anatomy and Physiology, School of Medicine, University of Padua, I-35121, Padua, Italy.
Aragona
F
F
Gottardo
L
L
Malendowicz
L K
LK
Nussdorfer
G G
GG
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism; D000313:Adrenal Medulla / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D005934:Glucagon / Q000494:pharmacology*; D006801:Humans; D010673:Pheochromocytoma / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D005934:Glucagon