Increased GH secretion in scrapie, a prion-associated neurodegenerative disease, is not due to suppressed IGF-1 negative feedback.
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.
Viguié
Catherine
C
UMR 181, INRA, ENVT 23 Chemin des Capelles, F-31076 Toulouse Cedex 3, France. c.viguie@envt.fr
Picard-Hagen
Nicole
N
Gayrard
Véronique
V
Toutain
Pierre-Louis
PL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D018592:Cross-Over Studies; D025461:Feedback, Physiological; D005838:Genotype; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012608:Scrapie / Q000378:metabolism / Q000503:physiopathology*; D012756:Sheep
D001786:Blood Glucose; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone