Hepatic growth hormone signaling in the late gestation fetal rat

The role of GH in the developing fetus is poorly understood. Several studie s have demonstrated a limited role for GH in late fetal life. In fact, few data are available regarding GH signal transduction in the late gestation f etus. We therefore focused on a comparison of hepatic GH signaling in near- term fetal rats [embryonic day 19 (E19)] and adult rats using a combination of in vitro studies employing hepatocytes in primary culture and in vivo s tudies. We found that GH receptor (GHr) binding was comparable in fetal liv er and adult liver. The long isoform of the GHr underwent tyrosine phosphor ylation in response to GH stimulation of E19 fetal hepatocytes in a manner similar to that seen in cultured adult hepatocytes. Furthermore, downstream signaling via the Janus kinase-a tyrosine kinase, STAT1 (signal transducer and activator of transcription), and STAT5 was also intact in both, as dem onstrated by the tyrosine phosphorylation of these signaling proteins. To c onfirm the relevance of these findings to the in vivo situation, GH was dir ectly administered by ip injection to E19 fetal and adult rats. In both cas es, tyrosine phosphorylation of STATE was markedly and rapidly induced. Fin ally, transfection of E19 fetal hepatocytes with GH-responsive reporter ele ments [Spi2.1(-275/+85)-CAT and 8xGHRE-TKCAT] demonstrated intact transcrip tional regulation. Our data indicate that GHr abundance and activity as wel l as downstream GH signaling are similar in the late gestation fetal rat an d in the adult and that these mechanisms appear capable of supporting physi ological GH functions in the developing liver.