Sex-specific regulation of body size and bone slenderness by the acid labile subunit - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Journal of Bone and Mineral Research Year : 2010

Sex-specific regulation of body size and bone slenderness by the acid labile subunit

Abstract

Insulin-like growth factor-1 (IGF-1) is a crucial mediator of body size and bone mass duringgrowth and development. In serum, IGF-1 is stabilized by several IGF-1 binding proteins(IGFBPs) and the acid labile subunit (ALS). Previous research using ALS knockout (ALSKO)mice indicated a growth retardation phenotype and clinical reports of humans have indicated shortstature and low bone mineral density (BMD) in patients with ALS deficiency. To determine thetemporal and sex-specific effects of ALS deficiency on body size and skeletal development duringgrowth we characterized control and ALSKO mice from 4 to 16 weeks of age. We found thatfemale ALSKO mice had an earlier onset reduction in body size (4 weeks), but that both femaleand male ALSKO mice were consistently smaller than control mice. Interestingly, skeletalanalyses at multiple ages showed increased slenderness of ALSKO femora that was more severe infemales than in males. Both male and female ALSKO mice appeared to compensate for their moreslender bones through increased bone formation on their endosteal surfaces during growth, butALSKO females had increased endosteal bone formation compared to ALSKO males. This studyrevealed age and sex-specific dependencies of ALS deficiency on body size and bone size. Thesefindings may explain the heterogeneity in growth and BMD measurements reported in humanALS deficient patients.
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Dates and versions

hal-02666501 , version 1 (31-05-2020)

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Victoria Demambro, Hayden-William Courtland, Jane Maynard, Hui Sun, Sébastien Elis, et al.. Sex-specific regulation of body size and bone slenderness by the acid labile subunit. Journal of Bone and Mineral Research, 2010, 25 (9), pp.2059-2068. ⟨10.1002/jbmr.94⟩. ⟨hal-02666501⟩

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