Evidence for the autocrine/paracrine regulation of tissue growth by the insulin-like growth factors

Many tissues can undergo tissue specific (local) growth in response to various stimuli. The objectives of this thesis were to investigate the local growth of skeletal muscle and brown adipose tissue and the possible involvement of the insulin-like growth factors (IGF-I and IGF-II) in regulating this growth in an autocrine/paracrine manner.;In Chapter 1, the effects of varying amounts of stretch stimulus on chicken skeletal muscle hypertrophy and atrophy were examined. The results indicated that the muscle hypertrophy response can be regulated by modulating the amount of time per day that the stretch stimulus is applied. In addition, intermittent stretch (for 4 hours/day) significantly inhibited regression of muscle atrophy.;In Chapters 2 and 3, the role of the IGFs in skeletal muscle growth was investigated. Compensatory hypertrophy of the plantaris and soleus muscles in normal (Chapter 2) and hypophysectomized (hypox; Chapter 3) rats was induced by cutting the tendon of the synergistic gastrocnemius muscle. Hypertrophy and IGF mRNA levels were then examined at 2, 4, and 8 days post-surgery. Significant hypertrophy was observed in both muscles in normal and hypox rats. IGF-I and IGF-II mRNA levels were elevated in hypertrophy muscles as compared to contralateral control muscles both in normal and hypox rats. The effects on IGF mRNA levels of rat growth hormone (rGH) administration to hypox rats was also investigated. IGF-I mRNA levels were elevated in the plantaris and soleus in response to rGH. These results indicate that IGF gene expression can be modulated by both systemic and local factors and suggest a role for the IGFs in autocrine/paracrine regulation of skeletal muscle growth.;In Chapter 4, the effects of (1) cold exposure of normal rats and (2) administration of rGH to hypox rats on IGF mRNA levels in rat brown adipose tissue (BAT) were investigated. IGF-I mRNA levels were high in BAT and were rGH dependent, but were not modulated by cold exposure. IGF-II mRNA levels were low and unaffected by rGH in BAT; however, exposure of rats to a cold environment appeared to increase IGF-II mRNA levels 2 to 3 fold in as little as 8 hours. A significant hyperplasia response was observed in BAT of rats exposed to the cold. These results suggest a potential autocrine/paracrine role for IGF-II in regulating BAT hyperplasia, although further studies on the IGF-II response in BAT are needed.