Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase.
Somatic mutations in the alpha-chain (alpha s) of the stimulatory regulatory protein of adenylyl cyclase (Gs) causing constitutive activation of the enzyme have been identified in a subset of human GH-secreting pituitary adenomas. This study reports on the differences between acromegalic patients bearing tumors without (group 1; n = 51) or with (group 2; n = 29) this alteration. No difference in age, sex, clinical features, duration of the disease, or cure rate was observed between the two groups. By contrast, group 2 patients had higher basal GH levels than group 1. Moreover, a significant difference in sellar morphology was found; group 2 patients more frequently showed sellas of normal size (grade I) than group 1. Hypersecretory activity of group 2 tumors was also apparent at electron microscopy; contrary to those of group 1, cells of group 2 tumors were densely granulated and showed prominent rough endoplasmic reticulum and Golgi complex. With respect to group 1, group 2 patients were less responsive to GH-releasing hormone, while they were more sensitive to somatostatin- and dopamine-induced GH inhibition. These results suggest that patients with constitutively active adenylyl cyclase have hyperactive tumors; the sensitivity of these tumors to inhibitory agents (somatostatin and dopamine), possibly counteracting the expression of activating mutations, might explain the low rate of tumor growth.
Spada
A
A
Institute of Endocrine Sciences, University of Milan, Italy.
Arosio
M
M
Bochicchio
D
D
Bazzoni
N
N
Vallar
L
L
Bassetti
M
M
Faglia
G
G
D000172:Acromegaly / Q000201:enzymology; D000236:Adenoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D003594:Cytoplasmic Granules / Q000473:pathology; D004298:Dopamine / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D006056:Golgi Apparatus / Q000473:pathology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009154:Mutation; D010911:Pituitary Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D012658:Sella Turcica / Q000473:pathology; D012969:Sodium Fluoride / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; D013973:Thyrotropin-Releasing Hormone; D012969:Sodium Fluoride; D013006:Growth Hormone; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D004298:Dopamine