Journal of Bone and Mineral Research vol:25 issue:3 pages:617-626
Abstract Although it is well established that males acquire more bone mass than females, the underlying mechanism and timing of this sex difference remain controversial. The aim of this study was to assess the relative contribution of sex steroid versus GH-IGF-I action to pubertal bone mass acquisition longitudinally in pubertal mice. Radial bone expansion peaked during early puberty (3-5 weeks of age) in male and female mice, with significantly more expansion in males compared to females (+40%). Concomitantly, in 5-week-old male versus female mice, periosteal and endocortical bone formation were higher (+70%) and lower (-47%), respectively, along with higher serum IGF-I levels during early puberty in male mice. In female mice, ovariectomy increased radial bone expansion during early puberty as well as the endocortical perimeter. In male mice, orchidectomy reduced radial bone expansion only during late puberty (5-8 weeks of age), while combined androgen and estrogen deficiency modestly decreased radial bone expansion during early puberty, accompanied by lower IGF-I levels. GHRKO mice with very low IGF-I levels, on the other hand, showed limited radial bone expansion and no skeletal dimorphism. From these data, we conclude that skeletal sexual dimorphism is established during early puberty and depends primarily on GH-IGF-I action. In males, androgens and estrogens have stimulatory effects on bone size during late and early puberty, respectively. In females, estrogens limit bone size during early puberty. These longitudinal findings in mice provide strong evidence that skeletal dimorphism is determined by independent and time-specific effects of sex steroids and IGF-I.