Growth hormone substitution increases gene expression of members of the IGF family in cortical bone from women with adult onset growth hormone deficiency--relationship with bone turn-over.
OBJECTIVE
To investigate the effects of growth hormone (GH) replacement therapy on bone matrix gene expression of insulin-like growth factors (IGFs) and markers of bone metabolism in women with adult-onset GH deficiency (GHD).


METHODS
Nineteen women, mean age 45 (range 24-56) years, were included in a double-blind, placebo-controlled parallel group study for 12 months. Biochemical markers were measured at baseline, 6 and 12 months. Bone biopsies were obtained and BMD was measured at baseline and after 12 months.


RESULTS
Maximum responses were observed after 6 and 12 months, for bone resorptive and bone formative markers respectively. GH therapy enhanced gene expression in cortical bone of IGFs, GH-and calcitonin-receptor (CR) and osteoprotegerin (OPG), however with the most pronounced effects on CR and IGF-I. Changes in IGF-I gene expression during longitudinal follow-up were significantly correlated with changes in both circulating IGF-I (r = 0.82, p < 0.05), changes in markers of enhanced osteoclastic activity, measured both locally in bone (CR, r = 0.87, p < 0.01) and in serum (CTX-I, r = 0.86, p < 0.05), as well as serum bone ALP (r = 0.96, p < 0.01).


CONCLUSIONS
This study indicates that both liver- and bone-derived IGF-I may be significant in mediating the effects of GH on bone metabolism in humans.
Ueland
T
T
Section of Endocrinology, Medical Department, National University Hospital, N-0027 Oslo, Norway. thor.ueland@klinmed.uio.no
Odgren
P R
PR
Yndestad
A
A
Godang
K
K
Schreiner
T
T
Marks
S C
SC
Bollerslev
J
J
D000328:Adult; D001483:Base Sequence; D016723:Bone Remodeling / Q000187:drug effects / Q000235:genetics; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000097:blood; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008875:Middle Aged; D053244:Osteoprotegerin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013002:Somatomedins / Q000235:genetics*
D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D013002:Somatomedins; C506030:TNFRSF11B protein, human; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D004247:DNA