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Title: Increased GH secretion in scrapie, a prion-associated neurodegenerative disease, is not due to suppressed IGF-1 negative feedback. Author: Viguié C, Picard-Hagen N, Gayrard V, Toutain PL. Journal: Domest Anim Endocrinol; 2009 Apr; 36(3):127-37. PubMed ID: 19179038. Abstract: GH secretion is increased in scrapie-diseased sheep. Although the role of the somatotropic axis as a neurotrophic and neuroprotective factor is well documented, no studies have been carried out on the mechanisms and functional significance of somatotropic perturbation in the pathophysiology of prion-associated neurodegenerative disease. The goal of this study was to test the hypothesis that increased GH secretion observed in a natural animal prion disease, scrapie, might reflect a general lack of action of IGF-1 and, more particularly, a suppressed IGF-1 negative feedback. The effect of human recombinant IGF-1 (rhIGF-1) on spontaneous and GHRH-induced secretions was studied in so-called "scrapie-resistant" and "scrapie sensitive" rams in vivo and in vitro on pituitary dissociated cells from both groups. The effect of rhIGF-1 infusion on spontaneous and GHRH-induced GH secretions was evaluated during the preclinical and clinical stages of the disease in vivo. Our results indicated that rhIGF-1 suppressed spontaneous GH secretion but not GHRH-induced secretion in vivo. RhIGF-1 had no effect on spontaneous and GHRH-induced GH secretion from dissociated pituitary cells. Clinical scrapie was associated with a significantly greater rhIGF-1-induced inhibition of GH spontaneous secretion (mean+/-S.E.M. inhibition of GH secretion: 31+/-8% vs. 45+/-4% in control and scrapie-affected rams, respectively). It can be concluded that the increase in GH secretion in scrapie-affected animals does not reflect a global lack of action of IGF-1. Further investigations are required to determine if other IGF-1 effects and more particularly neuroprotective mechanisms are altered in prion-associated neurodegenerative diseases.[Abstract] [Full Text] [Related] [New Search]