OBJECTIVE: Clinical @entity2012 is characterized by elevated GH secretion in the presence of high circulating @entity442 levels. We hypothesized that the physiological @entity442 /GH negative feedback loop may be reset in somatotroph @entity652 , specifically in terms of the level of expression of these receptors or mutations of the @entity9045 ( @entity9045 ) in such @entity5 . METHODS: We therefore investigated the full coding sequence of the @entity9045 in a series of somatotroph and other @entity977 . We also investigated the mRNA expression of these putative feedback receptors in a series of @entity977 and normal pituitary tissue, and their protein expression by immunostaining. Real-time RT-PCR assay was used for the quantification of the type 1 IGF receptor ( @entity2856 ) and @entity9045 ( @entity9045 ) mRNA, and sequence analysis was performed on the coding region of the @entity9045 gene. RESULTS: No somatic mutations of the @entity9045 mRNA were detected in 18 GH-secreting @entity5 or two nonfunctioning @entity977 (NFPAs). However, the levels of @entity9045 mRNA were significantly lower in both @entity5 and NFPAs compared to the normal pituitary (P < 0.05 for both). Immunostaining for @entity9045 also showed significantly less @entity9045 expression in somatotroph @entity652 compared to normal pituitary tissue (P < 0.0001). @entity2856 mRNA levels were significantly lower in @entity5 compared to normal pituitary (P = 0.005), and trended lower in corticotroph @entity5 (P = 0.07), while the other @entity5 types showed no significant difference from normal pituitary. Immunostaining for @entity2856 also showed less @entity2856 protein in the somatotroph @entity652 compared to the normal pituitary tissue (P < 0.01). CONCLUSIONS: Our findings suggest that decreased feedback inhibition of GH because of somatic mutations of the coding region of the @entity9045 are unlikely to be a common factor in the pathogenesis of these @entity5 . Nevertheless, decreased expression of the @entity9045 and of @entity2856 in @entity5 (both at the mRNA and protein level) may, at least in part, help explain the continuous secretion of GH from the @entity5 despite the high circulating levels of @entity442 and GH.

Reduced expression of the growth hormone and type 1 insulin-like growth factor receptors in human XXXX and an analysis of possible mutations of the growth hormone receptor.

@entity5 :: ('MESH:D009369', 'Disease') :: ['somatotroph tumours', 'tumours', 'tumour'] @entity442 :: ('3479', 'Gene') :: ['IGF-I'] @entity2856 :: ('3480', 'Gene') :: ['IGF-R'] @entity2012 :: ('MESH:D000172', 'Disease') :: ['acromegaly'] @entity977 :: ('MESH:D010911', 'Disease') :: ['pituitary adenomas'] @entity652 :: ('MESH:D000236', 'Disease') :: ['adenomas'] @entity9045 :: ('2690', 'Gene') :: ['GH-R', 'GH receptor']
@entity5 :: (MESH:D009369,Disease) :: ['somatotroph tumours']
