I think I figured out why extraneous IGF-1 looses its effectiveness. The body realizes there is additional IGF-1 in it so it increases cytosolic PLA2 levels to counter act the IGF-1. It must take weeks for the body to sense the need and produce enough cytosolic PLA2 to counter act the IGF-1, but once it does supplementing IGF-1 is useless.
"Generation of arachidonic acid by the ubiquitously expressed cytosolic phospholipase A2 (PLA2) has a fundamental role in the regulation of cellular homeostasis, inflammation and tumorigenesis. Here we report that cytosolic PLA2 is a negative regulator of growth, specifically of striated muscle. We find that normal growth of skeletal muscle, as well as normal and pathologic stress-induced hypertrophic growth of the heart, are exaggerated in Pla2g4a-/- mice, which lack the gene encoding cytosolic PLA2. The mechanism underlying this phenotype is that cytosolic PLA2 negatively regulates insulin-like growth factor (IGF)-1 signaling. Absence of cytosolic PLA2 leads to sustained activation of the IGF-1 pathway, which results from the failure of 3-phosphoinositide-dependent protein kinase (PDK)-1 to recruit and phosphorylate protein kinase C (PKC)-, a negative regulator of IGF-1 signaling. Arachidonic acid restores activation of PKC-, correcting the exaggerated IGF-1 signaling. These results indicate that cytosolic PLA2 and arachidonic acid regulate striated muscle growth by modulating multiple growth-regulatory pathways."
Here is the link: http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v9/n7/abs/nm891.html
Also the increase in IGF-1 decreased GH levels, which decrease natuaral IGF-1 levels.
"Growth hormone secretion is also part of a negative feedback loop involving IGF-1. High blood levels of IGF-1 lead to decreased secretion of growth hormone not only by directly suppressing the somatotroph, but by stimulating release of somatostatin from the hypothalamus"
Here is the link:
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/hypopit/gh.html
"Generation of arachidonic acid by the ubiquitously expressed cytosolic phospholipase A2 (PLA2) has a fundamental role in the regulation of cellular homeostasis, inflammation and tumorigenesis. Here we report that cytosolic PLA2 is a negative regulator of growth, specifically of striated muscle. We find that normal growth of skeletal muscle, as well as normal and pathologic stress-induced hypertrophic growth of the heart, are exaggerated in Pla2g4a-/- mice, which lack the gene encoding cytosolic PLA2. The mechanism underlying this phenotype is that cytosolic PLA2 negatively regulates insulin-like growth factor (IGF)-1 signaling. Absence of cytosolic PLA2 leads to sustained activation of the IGF-1 pathway, which results from the failure of 3-phosphoinositide-dependent protein kinase (PDK)-1 to recruit and phosphorylate protein kinase C (PKC)-, a negative regulator of IGF-1 signaling. Arachidonic acid restores activation of PKC-, correcting the exaggerated IGF-1 signaling. These results indicate that cytosolic PLA2 and arachidonic acid regulate striated muscle growth by modulating multiple growth-regulatory pathways."
Here is the link: http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v9/n7/abs/nm891.html
Also the increase in IGF-1 decreased GH levels, which decrease natuaral IGF-1 levels.
"Growth hormone secretion is also part of a negative feedback loop involving IGF-1. High blood levels of IGF-1 lead to decreased secretion of growth hormone not only by directly suppressing the somatotroph, but by stimulating release of somatostatin from the hypothalamus"
Here is the link:
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/hypopit/gh.html
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