Effects of Insulin-Like Growth Factors I and II on Growth and Differentiation of Transplanted Rat Embryos and Fetal Tissues*

The objective of our study was to obtain comparative information on the roles of insulin-like growth factors (IGFs) I and II in the growth and differentiation of rat embryos and fetuses in an in vivo experimental system. Ten-day-old rat embryos or 16-day-old fetal rat paws were transplanted under the capsule of both kidneys of syngeneic hosts, where they grew rapidly, and tissue differentiation occurred in an essentially normal manner. Infusion of a rabbit antiserum to human (h) IGF-I for 6 days into the renal artery of one kidney caused only a slight inhibition (approximately 20%) of growth of transplanted embryos on that kidney. However, 9 days of treatment with the antiserum caused highly significant growth retardation of transplanted embryos by 40-45%. Exposure of fetal paws to the same antiserum for 9 days inhibited their growth by 27%. Infusion of synthetic hIGF-II or partially purified rat IGF-II [(MSA)multiplication-stimulating activity], for 6 days stimulated the growth of embryo transplants directly, and MSA was more effective than hIGF-II. By contrast, infusion of purified natural hIGF-I did not promote their growth. Growth of fetal paw transplants in hypophysectomized (HX) hosts was reduced by 70% compared to that in intact hosts. In the HX hosts infusion of the MSA was more effective than the hIGF-I at promoting the growth of paw transplants. Both MSA and IGF-I promoted ossification in the fetal paws in the HX hosts. These results suggest that both IGFs could be involved in regulating the growth and differentiation in prenatal rats, and IGF-II may be the more effective of the two factors as a growth-promoting agent in utero.