Sexual dimorphism in cortical bone size and strength but not density is determined by independent and time-specific actions of sex steroids and IGF-1: evidence from pubertal mouse models.
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 growth hormone-insulin-like growth factor 1 (GH-IGF-1) action to pubertal bone mass acquisition longitudinally in pubertal mice. Radial bone expansion peaked during early puberty (3 to 5 weeks of age) in male and female mice, with significantly more expansion in males than in females (+40%). Concomitantly, in 5 week old male versus female mice, periosteal and endocortical bone formation was higher (+70%) and lower (-47%), respectively, along with higher serum IGF-1 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 to 8 weeks of age), whereas combined androgen and estrogen deficiency modestly decreased radial bone expansion during early puberty, accompanied by lower IGF-1 levels. GHRKO mice with very low IGF-1 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-1 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-1.
Callewaert
Filip
F
Center for Musculoskeletal Research, Leuven University Department of Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
Venken
Katrien
K
Kopchick
John J
JJ
Torcasio
Antonia
A
van Lenthe
G Harry
GH
Boonen
Steven
S
Vanderschueren
Dirk
D
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight; D015519:Bone Density; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000033:anatomy & histology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009929:Organ Size; D012737:Sex Factors; D012741:Sexual Maturation; D033081:Shear Strength / Q000502:physiology*; D013977:Tibia / Q000033:anatomy & histology; D013997:Time Factors
D000728:Androgens; D004967:Estrogens; D007334:Insulin-Like Growth Factor I