Longitudinal in vivo effects of growth hormone overexpression on bone in transgenic mice.
In this study we examined the effect of systemic overexpression of GH on bone in transgenic mice longitudinally in vivo over a period of 9 months. We observed substantially increased BMC in GH transgenic mice and a significant reduction in serum osteocalcin. GH effects on bone were strongly dependent on gender and developmental stage.


BACKGROUND
State-of-the-art bone marker and microimaging technology was applied in this longitudinal study to examine bone metabolism, BMC, bone density, and cortical bone structure over the life span of growth hormone (GH) transgenic (tg) mice.


METHODS
Thirty-eight mice from four genetic groups (male, female, tg, and controls) were examined with DXA, and their femur and tibia were examined with peripheral QCT (pQCT). Osteocalcin (formation) and collagen cross-links (resorption) from serum and urine were also measured at postnatal weeks 3, 6, 9, 12, 18, 26, and 38.


RESULTS
GH tg mice displayed a significant increase in body weight (up to 50%) and BMC (up to 90%), but serum osteocalcin was significantly reduced compared with controls. GH tg females (but not males) displayed increased trabecular density over controls up to week 12. In contrast, male (but not female) GH tg mice displayed a higher cortical cross-sectional area than controls. Cortical density was significantly lower in both male and female GH tg mice compared with control mice.


CONCLUSIONS
The increase in BMC in GH tg mice is associated with reduced serum osteocalcin levels, indicating that bone turnover may be lower than in the control mice. On a structural level, bone responds to GH excess in a gender-specific manner, with alterations varying substantially between different developmental stages.
Eckstein
Felix
F
Musculoskeletal Research Group, Institute of Anatomy, Ludwig-Maximilians-Universität, München, Germany. eckstein@anat.med.uni-muenchen.de
Weusten
Axel
A
Schmidt
Corina
C
Wehr
Ulrich
U
Wanke
Rüdiger
R
Rambeck
Walter
W
Wolf
Eckhard
E
Mohan
Subburaman
S
D000596:Amino Acids / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D015519:Bone Density; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000502:physiology; D002417:Cattle; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000254:growth & development / Q000378:metabolism; D013006:Growth Hormone / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015675:Osteocalcin / Q000097:blood; D011859:Radiography; D012737:Sex Factors; D013977:Tibia / Q000000981:diagnostic imaging / Q000254:growth & development / Q000378:metabolism; D013997:Time Factors
D000596:Amino Acids; D015675:Osteocalcin; C015484:pyridinoline; D013006:Growth Hormone; C036020:deoxypyridinoline