Molecular Mechanisms of Growth Hormone Induced Muscle Hypertrophy
Turner, Jeffrey Donald
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https://hdl.handle.net/2142/70052
Description
Title
Molecular Mechanisms of Growth Hormone Induced Muscle Hypertrophy
Author(s)
Turner, Jeffrey Donald
Issue Date
1987
Department of Study
Animal Sciences
Discipline
Animal Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Pathology
Abstract
The objective of these studies were three fold; (1) to determine the response of different aged rats to a growth hormone secreting tumor, (2) examine the presence and significance of extrahepatic insulin-like growth factor I (IGF-I) and IGF-II mRNA in rats bearing GH$\sb{3}$ tumors, and (3) evaluate the presence of oncogene mRNA in muscles from rats bearing GH$\sb{3}$ tumors and in myogenic cell lines.
Tumor producing GH$\sb{3}$ cells were introduced into Wistar-Furth rats of 3, 5, 18 and 24 months of age. After 7-8 weeks, all tumored animals had body weights at least 70% heavier than untreated control rats. Heart and hindlimb muscles were significantly (P $<$ 0.05) increased by 50-100% in tumored rats. Comparison among groups indicated that this muscle hypertrophy was attenuated in older animals. Somatomedin (=IGFs) levels, measured with a chick bioassay, were significantly (P $<$ 0.05) elevated in all tumored animals across age groups. The presence of GH$\sb{3}$ tumors were correlated with muscle hypertrophy and increased serum somatomedin.
The second study involved the molecular hybridization of specific IGF-I and IGF-II probes with RNA extracted from rat gastrocnemius and heart muscles. Specific IGF-I and IGF-II mRNA levels were low in these tissues in normal rats. The presence of GH$\sb{3}$ tumors was correlated with an 8 fold increase in IGF-I mRNA in gastrocnemius and a 3 fold increase in heart RNA. Levels of IGF-II mRNA were lower than those of IGF-I. Total RNA extracted from gastrocnemius and heart from tumored rats had a 4 fold increase in IGF-II abundance over control animals. Insulin-like growth factor-I was implicated in the local control of muscle hypertrophy.
Oncogenes are DNA sequences which encode proteins thought to be involved with the regulation of mitosis. Specific probes for the oncogenes abl, erb-B, fos, Ha-ras, Ki-ras, myc, mos, sis and src were hybridized to polyadenylated RNA from cultured muscle cells and growing gastrocnemius. Only the Ha-ras probe resulted in a detectable autoradiographic signal. The inappropriate size of the transcript and the presence of non-specific background make this observation tentative. The remaining oncogene probes did not result in measureable hybridization. Future research to determine the relationship between oncogenes and muscle growth must address the requirement for a more sensitive hybridization scheme.
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