XXXX causing @entity11125 in an 8-year old @entity1 : a possible pathogenetic mechanism.

@entity1 @entity2847 @entity3007 @entity2163 @entity7704 @entity10914 @entity5 @entity935 @entity1920 @entity11125 @entity876 @entity1218 @entity1943 @entity652 @entity413
The pathophysiology of @entity652 remains unclear. We studied a mammosomatotroph @entity652 removed from an 8-year old @entity1 with a 5-year history of growth acceleration and acromegalic @entity11125 at presentation. Elevated basal GH (mean 28 micrograms/l) and PRL (mean 120 micrograms/l) plasma levels were observed, as well as paradoxical responses of GH to L-dopa, @entity1218 and oral @entity413 administration; PRL was reduced by L-dopa and slightly increased by @entity1218 ; @entity7704 stimulated release of both GH and PRL. Two operations were required to remove the very large @entity5 and the @entity1 was treated with @entity2847 before the second. Hormonal secretion by @entity5 explants in culture was evaluated under basal conditions and after stimulation or inhibition. High levels of GH and PRL were secreted for up to 24 days. Furthermore, @entity7704 and @entity1218 caused a dose-related stimulation of both hormones, while @entity1943 and @entity935 were effective in suppressing either basal or stimulated hormone release only at very high (microM) concentrations. Intracellular events were studied by determination of the @entity3007 binding (G) protein levels and adenylate cyclase (AC) activity in the @entity5 tissue. Before @entity2847 treatment, AC activity was very high in the @entity5 and could be further stimulated by various agents; very high levels of the AC-stimulatory G protein alpha subunit @entity2163 and very low amounts of the AC-inhibiting G protein alpha subunit Gi3 alpha and of the phospholipase C-stimulating G protein alpha subunit Gq alpha were found in the @entity5 . After @entity2847 , baseline AC activity was normalized and could no longer be stimulated; @entity2163 and Gi3 alpha levels were unchanged while those of Gq alpha were normalized. Screening of @entity5 DNA after amplification by polymerase chain reaction followed by single-strand conformational polymorphism analysis did not reveal any mutations in the hot spots of G protein alpha subunits (alpha s, alpha i2, alpha o2 and alpha 11) genes or in the H-ras and @entity876 genes. @entity2163 and GH transcription factor-1 ( @entity10914 ) expression were evaluated by amplification of cDNA. While the mRNA expression of @entity10914 decreased after @entity2847 treatment, that of @entity2163 increased. These data suggest the possibility of an oncogenic process involving overexpression of @entity2163 , resulting in chronic activation of adenylate cyclase. Furthermore, our results suggest that the anti-secretory and anti-proliferative effects of @entity2847 may be mediated through a decrease in @entity10914 secondary to the inhibition of @entity1920 cyclase activity.
