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The Role of GH/IGF-I-Mediated Mechanisms in Sex Differences in Cortical Bone Size in Mice

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Abstract

Cortical bone dimensions are important determinants of bone strength. Gender differences in cortical bone size caused by greater periosteal expansion in males than in females during the pubertal growth spurt are well established both in humans and in experimental animal models. However, the mechanism by which gender influences cortical bone size is still a matter of investigation. The role of androgens and estrogen in pubertal bone growth has been examined in human disorders as well as animal models, such as gonadectomized or sex steroid receptor knockout mice. Based on the findings that growth hormone (GH) and insulin-like growth factor I (IGF-I) are major regulators of postnatal skeletal growth, we and others have predicted that sex hormones interact with the GH/IGF-I axis to regulate cortical bone size. However, studies conflict as to whether estrogen and androgens impact cortical bone size through the canonical pathway, through GH without IGF-I mediation, through IGF-I without GH stimulation, or independent of GH/IGF-I. We review recent data on the impact of sex steroids and components of the GH/IGF axis on sexual dimorphism in bone size. While the GH/IGF-I axis is a major player in regulating peak bone size, the relative contribution of GH/IGF-dependent mechanisms to sex differences in cortical bone size remains to be established.

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Acknowledgement

The authors thank Dr. Jon Wergedal for critically reading the manuscript. The work was supported by funding from the NIH (AR48139 to S. M.) and facilities provided by the Department of Veterans Affairs.

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  1. Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center and Loma Linda University, Loma Linda, CA, 92357, USA

    Lisa E. Olson & Subburaman Mohan

  2. University of Redlands, Redlands, CA, 92373, USA

    Lisa E. Olson

  3. Department of Internal Medicine, Center for Bone Research, University of Gothenburg, 41345, Göteborg, Sweden

    Claes Ohlsson

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  1. Lisa E. Olson
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Olson, L.E., Ohlsson, C. & Mohan, S. The Role of GH/IGF-I-Mediated Mechanisms in Sex Differences in Cortical Bone Size in Mice. Calcif Tissue Int 88, 1–8 (2011). https://doi.org/10.1007/s00223-010-9436-2

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