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Previously we have shown ( E. D. Adamson, M. J. Deller, and J. B. Warshaw, 1981 , Nature (London) 291, 656–659) that epidermal growth factor (EGF) binds specifically to the cells and stimulates the incorporation of tritiated thymidine into DNA of several tissues of mouse embryos in a dose-dependent fashion when tested in vitro. However, in vivo a different response is obtained; exogenous EGF causes reduced incorporation of radiolabeled thymidine compared to buffer-injected control embryos. Several possible explanations are being explored. Here we present evidence that one of the responses of embryonic tissues in vivo to exogenous EGF is “down-regulation” of its receptors.

We have investigated developmental profiles of ATP-dependent palmityl-CoA synthetase, acetyl-CoA synthetase, palmitylcarnitine transferase, and fatty acid oxidation in heart and liver of developing chicks and rats. Palmityl-CoA synthetase activity of rat liver and heart homogenates increased 6- to 10-fold during the first postnatal week. Chick embryo heart activity peaked between 13 and 16 days of development. The activity of embryonic chick livers was bimodal with highest activity seen at 7 and 16 days of development. Posthatching values were approximately 50–75% of the peak embryonic levels. Acetyl-CoA synthetase activity of rat liver and heart homogenates was low but also showed developmental increases following birth. Acetyl-CoA synthetase activity of chick embryonic hearts was greatest at 16 days of development. Palmitylcarnitine transferase activity of rat liver and heart homogenates showed a striking increase during the first week of life. Chick heart activity was similar to that observed for palmityl-CoA synthetase with a peak between 13 and 16 days of embryonic development. Coincident with the postnatal rise in fatty acid activation and palmitylcarnitine transferase activity in developing rats, the oxidation of palmityl-CoA plus carnitine and of palmitylcarnitine increased from barely measurable levels at birth to adult levels by 30 days of age. The increases that we observe probably relate to changes in the specific activity of the enzymes as well as to an increase in the absolute number of mitochondria during development.

We have investigated fatty acid synthesis by the developing heart. The only system for fatty acid synthesis in the heart is the mitochondrial elongation pathway. Myocardial fatty acid elongation was very low prenatally but increased rapidly during the first week of life. Coincident with weaning there was a sharp drop in elongation activity possibly related to a shift from the high fat intake provided by the milk to the carbohydrate diet provided by standard laboratory chow. Either NADH or NADPH could provide reducing equivalents for myocardial fatty acid elongation. The presence of a long-chain fatty acid primer in the medium resulted in a higher incorporation of acetyl-CoA throughout the developmental period. However, the ratio of endogenous fatty acid elongation activity to that in the presence of an added primer increased with age presumably in relation to the postnatal increase in the availability of long-chain fatty acid primers. Products of fatty acid elongation in postnatal rats included a range of saturated and unsaturated fatty acids with major peaks of stearic acid (18:0) and 20- and 22-carbon unsaturated fatty acids suggesting elongation of the palmityl-CoA primer by the-two carbon units of acetyl-CoA. Decarboxylation of fatty acid products indicated that all synthesis could be accounted for by chain elongation. The observed developmental changes in myocardial fatty acid elongation may be related to functional, structural, and nutritional adaptations of the cell to the postnatal environment.