Hepatic growth hormone signaling in the late gestation fetal rat.
The role of GH in the developing fetus is poorly understood. Several studies 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 fetus. 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 studies. We found that GH receptor (GHr) binding was comparable in fetal liver and adult liver. The long isoform of the GHr underwent tyrosine phosphorylation 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-2 tyrosine kinase, STAT1 (signal transducer and activator of transcription), and STAT5 was also intact in both, as demonstrated by the tyrosine phosphorylation of these signaling proteins. To confirm the relevance of these findings to the in vivo situation, GH was directly administered by ip injection to E 19 fetal and adult rats. In both cases, tyrosine phosphorylation of STAT5 was markedly and rapidly induced. Finally, transfection of E19 fetal hepatocytes with GH-responsive reporter elements [Spi2.1(-275/+85)-CAT and 8xGHRE-TKCAT] demonstrated intact transcriptional regulation. Our data indicate that GHr abundance and activity as well as downstream GH signaling are similar in the late gestation fetal rat and in the adult and that these mechanisms appear capable of supporting physiological GH functions in the developing liver.
Phornphutkul
C
C
Department of Pediatrics, Brown University and Rhode Island Hospital, Providence 02903, USA.
Frick
G P
GP
Goodman
H M
HM
Berry
S A
SA
Gruppuso
P A
PA
D000375:Aging / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D005333:Fetus / Q000378:metabolism / Q000502:physiology*; D005865:Gestational Age; D013006:Growth Hormone / Q000502:physiology*; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D007274:Injections, Intraperitoneal; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D011986:Receptors, Somatotropin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494081:Stat1 protein, rat; D015534:Trans-Activators; D019382:Human Growth Hormone; D014443:Tyrosine; D013006:Growth Hormone