Anabolic effects of rhIGF-I/IGFBP-3 in vivo are influenced by thyroid status.
BACKGROUND
There are close interrelationships between hormones that regulate bone formation and protein biosynthesis. For example, growth hormone and thyroid hormones can influence plasma levels of insulin-like growth factor-I (IGF-I). A patient's status regarding hormones other than IGF-I may thus indirectly modify the efficacy of IGF-I treatment. The aim of the current study was to determine if a statistical method could be used to identify key endocrine variables controlling an individual's response to IGF-I treatment.


METHODS
Biochemical profiles from the somatotropic, thyroid and adrenal axes were determined on two separate occasions in two different study cohorts. Each cohort was divided into four groups: placebo, low, medium and high dose of recombinant human IGF-I/IGF binding protein-3 (rhIGF-I/IGFBP-3). The relative changes in collagen C-terminal peptide (CICP) levels were explained as a function of the basal endocrine profile of each treated individual. This relationship was further examined in an experimental rat model, where undernourished rats were rendered hypothyroid by propylthiouracil and subsequently treated with rhIGF-I/IGFBP-3.


RESULTS
The results of our statistical analysis in both cohorts indicated that each subject's response to rhIGF-I/IGFBP-3 administration was controlled in part by the individual's thyroid status prior to drug administration (r = 0.78 for both cohorts). The results from the animal study revealed that IGF-I treatment stimulated muscle protein synthesis by 35 +/- 9% (P = 0.05) in euthyroid rats but not in hypothyroid rats.


CONCLUSIONS
The relationship between endocrine axes is not simple. An improved understanding of the interactions between neuroendocrine systems may facilitate the design of efficient drug regimens in the treatment of diseases such as osteoporosis and muscle wasting.
Svanberg
E
E
Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.Elisabeth.Svanberg@serono.com
Healey
J
J
Mascarenhas
D
D
D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003094:Collagen / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*
D015415:Biomarkers; D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D003094:Collagen