Overexpression of human hydroxysteroid (17beta) dehydrogenase 2 induces disturbance in skeletal development in young male mice.
To understand the function of human hydroxysteroid (17beta) dehydrogenase 2 (HSD17B2) in the peripheral tissues in vivo, we studied the bone development in transgenic male mice ubiquitously expressing human HSD17B2. Bones of HSD17B2TG and WT males (26 days and 2 and 6 mo old) were analyzed by pQCT and histomorphometry, and data were correlated with serum testosterone (T), IGF-I, and osteocalcin concentrations. At the age of 26 days, the body weight of HSD17B2TG males was significantly lower, and the lengths of the tibia and femur of the HSD17B2TG males were significantly shorter. Histomorphometric and pQCT analyses showed lower trabecular and cortical BMD, a markedly smaller area of cortical bone at both of the diaphyses, and a smaller percentage of trabecular bone volume and thickness in the HSD17B2TG males. The data suggested slower osteoblast differentiation and a slower bone formation rate of femoral diaphysis on the periosteum but faster on the endocortical surface in HSD17B2TG males. The altered bone parameters were correlated with low serum T, IGF-I, and osteocalcin concentrations at the prepubertal age. Interestingly, after puberty, the bone parameters analyzed in the adult HSD17B2TG males were mostly normal, consistent with the normal body weight and normalized serum concentrations of IGF-I and T. In conclusion, HSD17B2TG males presented with growth retardation and a decreased bone formation rate at prepubertal age. These changes were associated with lower serum IGF-I, osteocalcin, and T concentrations. It is concluded that the enforced constitutive expression of HSD17B2 disturbs the coordinated action of IGF-I and sex steroids essential for pubertal bone growth.
Shen
ZhongYi
Z
Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
Peng
ZhiQi
Z
Sun
Yi
Y
Väänänen
H Kalervo
HK
Poutanen
Matti
M
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D001835:Body Weight; D001846:Bone Development; D002454:Cell Differentiation / Q000235:genetics; D004960:Estradiol Dehydrogenases; D005269:Femur / Q000473:pathology; D005786:Gene Expression Regulation; D006132:Growth Plate / Q000473:pathology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood; D013977:Tibia / Q000473:pathology; D014057:Tomography, X-Ray Computed
D015415:Biomarkers; D015675:Osteocalcin; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D015067:17-Hydroxysteroid Dehydrogenases; D004960:Estradiol Dehydrogenases; C523763:HSD17B2 protein, human