Cumulative effects of lifelong systemic excess growth hormone on postcranial skeletal morphology in adult mice

Abstract

Many developmental and metabolic effects of growth hormone (GH) on vertebrate life history traits have been widely studied in biological and biomedical contexts. The scope of alterations in GH/GH receptor (GHR) interactions has generally focused on molecular, cellular, histological, and physiological framing, leaving a gap in understanding of how the cumulative organism‐ and lifespan‐scale manifestations of morphological changes attributable to GH/GHR perturbations may both be influenced by and also influence smaller‐scale study results. The pilot study conducted herein used micro‐computed tomography (μCT) to survey and characterize the axial and appendicular skeletons of adult male and female bGH (transgenic overexpression of bovine GH) mice and to compare them with those of age‐ and sex‐matched wild‐type (WT) controls. Male and female bGH mice in our sample were larger (by linear measurements of skeletal elements) and leaner but not heavier than their WT counterparts. bGH mice exhibit thoracic kyphosis and radiographically detectable incipient sacralization of the last lumbar vertebra, as well as robust and altered muscle attachment sites in both girdle and long bones, re‐orientation of the acetabulum, and dysmorphology of the femur at both hip and knee joints. bGH mice generally lack clear, radiologically determinable differentiation of long bone growth plates and bear larger and differently proportioned sesamoids at the elbow and knee. They are also preferentially subject to the accumulation of inferred heterotopic calcification (IHC) and other radiodense soft tissue (RST) around joints and entheses. Female bGH mice exhibit variable and aberrant morphology in the humerus, innominate, and femur not seen in other groups, and show the most size and shape variation within the four genotype × sex groupings. Our survey illustrates widespread musculoskeletal impacts of excessive GH into adulthood in the model. These data provide an initial whole‐skeleton framework for further efforts characterizing molecular‐, cellular‐, and tissue‐scale alterations ultimately influencing the bGH mouse model skeletal phenotype. This pilot work serves to contextualize future preclinical studies as well as broader investigations into how GH and its metabolic cascade may affect vertebrate morphological and histological development, shape and size disparity, and dimorphism.