title: Prepubertal OVX increases IGF-I expression and bone accretion in C57BL/6J mice.
abstract: It is generally well accepted that the pubertal surge in estrogen is responsible for the rapid bone accretion that occurs during puberty and that this effect is mediated by an estrogen-induced increase in growth hormone (GH)/insulin-like growth factor (IGF) action. To test the cause and effect relationship between estrogen and GH/IGF, we evaluated the consequence of ovariectomy (OVX) in prepubertal mice (C57BL/6J mice at 3 wk of age) on skeletal changes and the GH/IGF axis during puberty. Contrary to our expectations, OVX increased body weight (12-18%), bone mineral content (11%), bone length (4%), bone size (3%), and serum, liver, and bone IGF-I (30-50%) and decreased total body fat (18%) at 3 wk postsurgery. To determine whether estrogen is the key ovarian factor responsible for these changes, we performed a second experiment in which OVX mice were treated with placebo or estrogen implants. In addition to observing similar results compared with our first experiment, estrogen treatment partially rescued the increased body weight and bone size and completely rescued body fat and IGF-I levels. The increased bone accretion in OVX mice was due to increased bone formation rate (as determined by bone histomorphometry) and increased serum procollagen peptide. In conclusion, contrary to the known estrogen effect as an initiator of GH/IGF surge and thereby pubertal growth spurt, our findings demonstrate that loss of estrogen and/or other hormones during the prepubertal growth period effect leads to an increase in IGF-I production and bone accretion in mice.
authors.affiliation: Jerry L. Pettis Memorial Veterans Affairs Medical Center, Loma Linda, California 92357, USA.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Govoni
authors.forename: Jon E
authors.initials: JE
authors.lastname: Wergedal
authors.forename: Robert B
authors.initials: RB
authors.lastname: Chadwick
authors.forename: Apurva K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: Subburaman
authors.initials: S
authors.lastname: Mohan
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001846:Bone Development / Q000502:physiology*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D010052:Ovariectomy; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation / Q000502:physiology*; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D004967:Estrogens; D018975:Insulin-Like Growth Factor Binding Protein 5; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D007334:Insulin-Like Growth Factor I