Gender differences in the response of CD-1 mouse bone to parathyroid hormone: potential role of IGF-I.
Parathyroid hormone (PTH) exerts both catabolic and anabolic actions on bone. Studies on the skeletal effects of PTH have seldom considered the effects of gender. Our study was designed to determine whether the response of mouse bone to PTH differed according to sex. As a first step, we analyzed gender differences with respect to bone mass and structural properties of 4 month old PTH treated (80 microg/kg per day for 2 weeks) male and female CD-1 mice. PTH significantly increased fat free weight/body weight, periosteal bone formation rate, mineral apposition rate, and endosteal single labeling surface, while significantly decreasing medullary area in male mice compared with vehicle treated controls, but induced no significant changes in female mice. We then analyzed the gender differences in bone marrow stromal cells (BMSC) isolated from 4 month old male and female CD-1 mice following treatment with PTH (80 microg/kg per day for 2 weeks). PTH significantly increased the osteogenic colony number and the alkaline phosphatase (ALP) activity (ALP/cell) by day 14 in cultures of BMSCs from male and female mice. PTH also increased the mRNA level of receptor activator of nuclear factor kappaB ligand in the bone tissue (marrow removed) of both females and males. However, PTH increased the mRNA levels of IGF-I and IGF-IR only in the bones of male mice. Our results indicate that on balance a 2-weeks course of PTH is anabolic on cortical bone in this mouse strain. These effects are more evident in the male mouse. These differences between male and female mice may reflect the greater response to PTH of IGF-I and IGF-IR gene expression in males enhancing the anabolic effect on cortical bone.
Wang
Yongmei
Y
Department of Medicine, Endocrine Unit, Veterans Affairs Medical Center, University of California, San Francisco, California 94117-1080, USA.
Sakata
Takeshi
T
Elalieh
Hashem Z
HZ
Munson
Scott J
SJ
Burghardt
Andrew
A
Majumdar
Sharmila
S
Halloran
Bernard P
BP
Bikle
Daniel D
DD
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D010281:Parathyroid Hormone / Q000378:metabolism* / Q000494:pharmacology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D017526:Receptor, IGF Type 1 / Q000032:analysis; D012737:Sex Factors; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013977:Tibia
D015415:Biomarkers; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D000469:Alkaline Phosphatase