摘要：

Growth hormone (GH) is the second variable that regulates IGF-I synthesis and secretionbut for the liver to respond to growth hormone with normal IGF-I synthesis requiresadequate nutrition. GH is a potent stimulant of IGF-I synthesis and GH administration to GH deficient animals results in a brisk increase in IGF-I gene transcription in the liver that leads to a major increase in serum IGF-I (10). The increase in serum IGF-I then feeds back on the pituitary gland to suppress GH secretion and maintain homeostasis. IGF binding proteins are another variable which regulates serum IGF-I concentrations. There are six IGF bindingproteins (11). IGFBP-3 is the principal binding protein in serum and its concentration is also increased in response to GH and this change accounts for a significant fraction of theincrease in total IGF-I that occurs in response to GH. The increase in IGFBP-3 in responseto GH is also modulated by changes in nutrition. When IGF-I is bound to IGFBP-3 thebinary complex binds to a third protein termed acid labile subunit or ALS. ALSconcentrations are also GH dependent (12). This ternary complex prolongs the half life ofIGF-I in serum from less than 5 min to 16 hrs. IGFBP-5 is much less abundant thenIGFBP-3 but it also binds to ALS and its concentration increases in response to GH. Thuschanges in IGFBP-3, IGFBP-5 and ALS all function to increase the serum IGF-Iconcentration by prolonging its half life. Two other IGF binding proteins, IGFBP-1, and -2 do not bind to ALS and therefore only prolong the half life of IGF-I to periods rangingbetween 90 min and 2 hr. Therefore they have minimal effects in increasing total serumIGF-I concentrations. However the regulation of serum concentrations of these proteins isimportant for regulating IGF-I actions. Under normal circumstances IGFBP-3 and 5 aresaturated. Therefore abrupt changes in IGFBP-1 and -2 which are not saturated and whichoccur as a result of changes in either nutrient intake or insulin secretion, can result in major changes in free IGF-I and thereby regulate tissue responsiveness (13). Other hormones that regulate IGF-I bioactivity include cortisol which antagonizes the actions of IGF-I andtherefore can result in an increase in serum concentrations, and thyroxine which is necessary for normal IGF-I biosynthesis and which can stimulate an increase in IGF-I concentrationsin hyperthyroidism. Estrogens function to antagonize the ability of growth hormone tostimulate IGF-I synthesis in the liver and testosterone alters IGF binding proteinconcentrations. Additionally the growth hormone analog, human placental growth hormone is an important stimulant of IGF-I synthesis in pregnancy. All of these hormones functioncoordinately with changes in nutrient intake to modulate the ability of IGF-I to regulate both growth and metabolism.

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