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Major Hypercorticism Is an Endocrine Feature of Ewes with Naturally Occurring Scrapie

Unité associée INRA de Physiopathologie et Toxicologie Expérimentales (V.G., N.P.-H., C.G., J.G., P.L.T.) Ecole Nationale Vétérinaire de Toulouse, 31076 Toulouse, France; Laboratoire de Neuroendocrinologie Expérimentale (M.G., N.S.), Institut National de la Santé et de la Recherche Médicale U501, 13326 Marseille, France; and Unité associée INRA de Physiopathologie Respiratoire des Ruminants (O.A., F.S.), Ecole Nationale Vétérinaire de Toulouse, 31076 Toulouse, France

Address all correspondence and requests for reprints to: P. L. Toutain, Laboratoire de Physiologie & Thérapeutique, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse. E-mail: pl.toutain{at}envt.fr

The aim of this study was to identify the origin of scrapie-induced hypercortisolism. Cortisol and ACTH kinetics and production rate were measured in 14 ewes (6 healthy and 8 scrapie-affected). It was shown that cortisol plasma clearance remained unmodified but that cortisol production rate and plasma concentrations of free cortisol were increased by a factor of 5, whereas the total cortisol plasma concentrations were only doubled. The apparent discrepancy between adrenal secretion rate and the corresponding total cortisol plasma levels was attributable to the scrapie-induced lower corticosteroid-binding globulin (CBG) binding capacity, which altered the ratio of free-to-bound cortisol. The secretion rate of ACTH from diseased ewes was increased by a factor of 1.5, in comparison with healthy ewes, and 4 of the 8 scrapie-affected ewes exhibited a decreased response to a low dexamethasone suppression test. The administration of tetracosactide induced a 2-fold increase in the cortisol production in diseased ewes, compared with that of healthy ewes, but the pituitary sensitivity to ovine CRF was not modified by the prion disease.

In conclusion, natural scrapie displays a syndrome of hypercorticism associated with increased ACTH secretion, hyperresponsiveness of the adrenals, and lower CBG binding capacity, which leads to overexposure to CBG-free cortisol.

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