Discussion 5

P.D. Gluckman G. A . Werther (Victoria, Australia): The concept of a fetal paracrinelautocrine system for IGF-I has been discussed for the rat and for humans. What is the major source of circulating IGF-I in fetal sheep and how does what you have discussed tie in with the concept of a fetal paracrine system, particularly in growing tissues? Could one or several GHs be acting in these tissues? Do we know anything about the receptors in these areas? P. D. Gluckman (Auckland, New Zealand): Many fetal tissues synthesize IGF-I. There is a correlation of IGF-I synthesis with liver size, which suggests that the liver may be one important source. I was not trying to address the controversy of endocrine versus paracrine control of skeletal growth; however I do think that IGF-I could be working via the circulation, either by acting on the placenta to drive nutrient availability or through a direct action on the skeletal system. GH receptors are present in other tissues. Functional GH receptors have been found in fetal pancreas and adrenal glands; however, GH does not appear to be involved in fetal somatic growth. Cytosolic GH-binding proteins have been found in the fetal brain, but whether there are any receptors on the cell surface remains to be resolved.