Linkage between growth retardation and pituitary cell morphology in a dystrophin-deficient pig model of Duchenne muscular dystrophy. (April 2020)

• Record Type: Journal Article
• Authors: Hofmann, I.; Kemter, E.; Theobalt, N.; Fiedler, S.; Bidlingmaier, M.; Hinrichs, A.; Aichler, M.; Burkhardt, K.; Klymiuk, N.; Wolf, E.; Wanke, R.; Blutke, A.
• Is Part Of: Growth hormone & IGF research. Volume 51(2020)
• Page Start: 6
• Page End: 16
• Publication Date: 2020-04
• Subjects: Adenohypophysis -- Disector -- Growth hormone (GH) -- Quantitative stereology -- Short stature; A Area -- AA Area density -- ACID Acidophil cells -- AH Adenohypophysis -- BCA Bicinchoninic acid protein assay -- BMBF Federal Ministry of Education and Research -- BRW Brain Weight -- BW Body Weight -- DMD Duchenne Muscular Dystrophy -- FFPE Formalin Fixed Paraffin Embedded -- fs Linear tissue shrinkage factor -- GH Growth Hormone -- GRMD Golden Retriever Muscular Dystrophy -- IGF1 Insulin-like Growth Factor 1 -- IUR Isotropic Uniform Random -- Mdx dystrophin-deficient mice -- N Number -- NH Neurohypophysis -- NV Numerical volume density -- PG Pituitary Gland -- PGW Pituitary Gland Weight -- P.INTERM Pars intermedia -- Pt Points -- PTPT Point density -- Q− Counted particles -- SOM Somatotroph cells -- 1SOM Single somatotroph cell -- SUR Systematic Uniform Random -- V Volume -- VV Volume density -- WT Wild Type; Growth regulators -- Periodicals; Growth -- Regulation -- Periodicals; Somatomedin -- Periodicals; Somatomedins -- Periodicals; Growth Hormone -- Periodicals; Growth Substances -- Periodicals; Croissance -- Régulation -- Périodiques; Croissance -- Régulateurs -- Périodiques; Somatotrophine -- Périodiques; Somatomédine -- Périodiques; Growth -- Regulation; Growth regulators; Electronic journals; Periodicals; Electronic journals; 612.4
• DOI: 10.1016/j.ghir.2019.12.006
• Languages: English
• ISSNs: 1096-6374

Abstract

Abstract: 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. Highlights: Short stature is common in human DMD but the role of GH/IGF1 is still uncertain. DMD pigs represent a well-established large animal model of DMD. DMD pigs have proportionally reduced somatotroph numbers. The total volume of GH-granules per somatotroph cell was unchanged in DMD pigs. The study shows no evidence for a role of somatotrophs in growth failure of DMD pigs.