REGULATION OF SERUM INSULIN-LIKE GROWTH FACTOR-I (IGF-I), HEPATIC GROWTH-HORMONE BINDING AND IGF-I GENE-EXPRESSION IN THE RAT DURING PREGNANCY AND LACTATION

An apparent GH resistance occurs in pregnancy, since GH concentrations in serum are reported to be normal or elevated, whereas serum IGF-I f alls to very low levels. To determine whether this GH resistance is ma nifest at the level of the hepatic GH receptor or in the ability of GH to initiate IGF-I gene expression, we have determined hepatic IGF-I m RNA expression, circulating IGF-I and hepatic GH binding during variou s stages of pregnancy and lactation in the rat. The concentration of I GF-I in serum fell from 37 +/- 5 nmol/l (means +/- S.E.M.) in virgin r ats to 17 +/- 1 nmol/l in rats in late pregnancy, recovered in early l actation (31 +/- 3 nmol/l) but was again significantly lower than in v irgin animals by mid-lactation (22 +/- 3 nmol/l). Hepatic GH binding d id not vary significantly during pregnancy but showed a small signific ant decrease in early lactation when expressed per mg membrane protein . When expressed as GH binding per liver, however, there were no signi ficant changes in GH binding at any stage. Liver weight increased sign ificantly between virgin and early pregnant animals (7.1 +/- 0.2 g com pared with 9.2 +/- 0.5 g respectively, P<0.01) and continued to increa se up to late lactation (14.3 +/- 0.4 g). Similarly, although the amou nt of IGF-I gene expression/unit RNA declined in late pregnant when co mpared with virgin animals (6.0 +/- 0.6 versus 3.4 +/- 0.4 arbitrary o ptical density units respectively, P<0.05), when the increase in liver weight and RNA content during pregnancy was taken into account there was actually a steady increase in IGF-I gene expression per total live r throughout both pregnancy and lactation, the difference becoming sig nificant by mid-lactation (P<0.05). Thus, when the changes in liver we ight which take place during pregnancy and lactation are taken into ac count we conclude that any hepatic resistance to GH in late pregnancy and lactation must be a post-receptor event which is mitigated in larg e part by increase in liver size, cell number and RNA content.