Previous measurements of somatomedins (Sms) and insulin-like growth factors (IGFs) in maternal and fetal serum have yielded contradictory results. We have, therefore, measured maternal, fetal, and neonatal rat serum with two highly specific assays: 1) IGF-I/Sm-C RiA and 2) a highly specific IGF-II/rat placental membrane radioreceptor assay (RRA). In addition, we have made measurements with a less specific multiplication-stimulating activity (MSA)-rat placental membrane RRA. To avoid possible serious artifacts created by Sm-binding proteins, preliminary acid-ethanol extraction of serum was performed. Results are expressed in terms of a reference human serum with an assigned potency of 1 U/ml. Maternal RIA IGF-I fluctuated between 1.1-1.4 U/ml from the 17th day of pregnancy to the 25th day after delivery (nonpregnant rat serum pool, 1.25 +/- 0.22 U/ml). On day 21 of gestation, fetal serum radioimmunoassayable IGF-I was 1.03 +/- 0.03 U/ml. After birth, radioimmunoassayable IGF-I fell and reached .19 +/- 0.03 U/ml at 18 days of age, but rose to 0.71 +/- 0.04 U/ml at 25 days of age. At term, maternal radioreceptor assayable IGF-II was 2.18 +/- 0.27 U/ml (nonpregnant female pool, 1.4 +/- 0.12). By the 25th postpartum day, radioreceptor assayable IGF-II was 1.39 +/- 0.12 U/ml. Radioreceptor assayable IGF-II in fetal serum on day 19 was 3.26 +/- 0.48 U/ml and rose to 5.37 +/- 0.66 U/ml on the day of delivery. A further rise to 8.92 +/- 1.03 occurred on day 5. A subsequent fall to 2.41 +/- 0.05 U/ml was observed on day 25. The patterns of results of the MSA RRA in fetal and neonatal rat serum were similar to that obtained with the IGF-II RRA. We now conclude that radioimmunoassayable IGF-I is present in higher concentrations than previously reported in term fetal rat serum and that radioreceptor assayable IGF-II is selectively elevated in rat fetal and neonatal life and may have unique metabolic and growth-promoting significance.U

A B S T R A C T Alcohol feeding to rats produced hepatomegaly, associated with enlargement of the hepatocytes. The increase in liver dry weight was accounted for not only by fat but also by protein accumulation, primarily in microsomes and cytosol, with a selective increase in export proteins: concentrations of both immunoreactive albumin and transferrin were augmented in liver microsomes and cytosol of ethanol-fed rats. To investigate the mechanism ofthis protein accumulation, [14C]leucine was injected intravenously and its incorporation into both liver and serum proteins was measured after various time intervals. Rates of synthesis and export were assessed from protein labeling and specific activities of leucyl-tRNA. Synthesis of liver protein and proalbumin were enhanced by chronic ethanol feeding, but this was not associated with a corresponding rise in serum albumin output. Actually, there was a significant retention of the label in liver albumin and transferrin with delayed appearance in the serum of ethanol-fed rats. This indicated that, regardless of the changes in synthesis, the export of protein from the liver into the plasma was impaired. This alteration in export was associated with a decreased amount of polymerized tubulin in the liver of ethanol-treated animals. Thus, both enhanced protein synthesis and defective export contribute to the ethanol-induced accumulation of liver protein, and the decrease in liver microtubules represents a possible site for impairment of protein export.

The hepatomegaly that appears after long-term feeding of ethanol results in accumulation of protein that is quantitatively as important as the increase in lipid. The bulk of protein accumulated in the soluble fraction of the cell. Hepatic albumin and transferrin concentrations increase and colchicine-binding protein decreases, thus suggesting an intrahepatic retention of export proteins.