MATURATIONAL CHANGES OF INSULIN BINDING TO FETAL HEPATOCYTES

Abstract

To determine if the reported lack of direct insulin netabolic effects in fetal tissues is due to alterations in hormone binding and/or processing, we characterized the binding, internalization, and degradation of insulin by cultured hepatocytes from rat fetuses of 17, 19, and 21 days gestation. When insulin (100 nM) was incubated with fetal hepatocytes, we observed substantial reductions (66%-100%) in immunoreactive insulin. This loss was greatest in cultures prepared from 19 day fetuses. 125I-Insulin binding at 37 C rapidly reached a peak at 30 min. Specific binding was greatest in 19 day cells; 460 fmole/mg protein compared to 150 and 190 fmole/mg protein in 17 and 21 day fetal hepatocytes, respectively. Prior exposure to insulin (100 nM) induced an inhibition of subsequent binding, increasing with gestational age. Only minimal down-regulation was detectable in 17 day hepatocytes. Both internalization and intracellular degradation of 125I-insulin occurred rapidly, following a similar time course for all three ages. Despite the ability of 17 day fetala hepatocytes to bind, internalize, and degrade insulin, we were unable to demonstrate receptor down-regulation. The dissociation of these related processes raises the possibility that these cells have a more rapid rate of receptor turnover than those from 19 and 21 day fetuses.