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Hofmann, I.* ; Kemter, E.* ; Theobalt, N.* ; Fiedler, S.* ; Bidlingmaier, M.* ; Hinrichs, A.* ; Aichler, M. ; Burkhardt, K.* ; Klymiuk, N.* ; Wolf, E.* ; Wanke, R.* ; Blutke, A.

Linkage between growth retardation and pituitary cell morphology in a dystrophin-deficient pig model of Duchenne muscular dystrophy.

Growth Horm. IGF Res. 51, 6-16 (2020)

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Open Access Green as soon as Postprint is submitted to ZB.

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Objective: Human patients with Duchenne muscular dystrophy (DMD) commonly exhibit a short stature, but the pathogenesis of this growth retardation is not completely understood. Due to the suspected involvement of the growth hormone/insulin-like growth factor 1 (GH/IGF1) system, controversial therapeutic approaches have been developed, including both GH- administration, as well as GH-inhibition. In the present study, we examined relevant histomorphological and ultrastructural features of adenohypophyseal GH-producing somatotroph cells in a porcine DMD model.Methods: The numbers and volumes of immunohistochemically labelled somatotroph cells were determined in consecutive semi-thin sections of plastic resin embedded adenohypophyseal tissue samples using unbiased state-of-the-art quantitative stereological analysis methods.Results: DMD pigs displayed a significant growth retardation, accounting for a 55% reduction of body weight, accompanied by a significant 50% reduction of the number of somatotroph cells, as compared to controls. However, the mean volumes of somatotroph cells and the volume of GH-granules per cell were not altered. Western blot analyses of the adenohypophyseal protein samples showed no differences in the relative adenohypophyseal GH-abundance between DMD pigs and controls.Conclusion: The findings of this study do not provide evidence for involvement of somatotroph cells in the pathogenesis of growth retardation of DMD pigs. These results are in contrast with previous findings in other dystrophin-deficient animal models, such as the golden retriever model of Duchenne muscular dystrophy, where increased mean somatotroph cell volumes and elevated volumes of intracellular GH-granules were reported and associated with DMD-related growth retardation. Possible reasons for the differences of somatotroph morphology observed in different DMD models are discussed.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Adenohypophysis ; Disector ; Growth Hormone (gh) ; Quantitative Stereology ; Short Stature; Short Stature; Hormone; Expression; Secretion; Mazindol; Efficacy; Mouse; Pathology; Patient; Lesions

ISSN (print) / ISBN 1096-6374

e-ISSN 1096-6374

Journal Growth Hormone and IGF Research

Quellenangaben Volume: 51, Pages: 6-16

Publisher Elsevier

Publishing Place Journal Production Dept, Robert Stevenson House, 1-3 Baxters Place, Leith Walk, Edinburgh Eh1 3af, Midlothian, Scotland

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Analytical Pathology (AAP)