Hepatic Growth Hormone Signaling in the Late Gestation Fetal Rat1

• Published in: Endocrinology (Philadelphia) Vol. 141; no. 10; pp. 3527 - 3533
• Main Authors: Phornphutkul, Chanika, Frick, G. Peter, Goodman, H. Maurice, Berry, Susan A, Gruppuso, Philip A
• Format: Journal Article
• Language: English
• Published: Endocrine Society 01-10-2000
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.141.10.7702

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 E19 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.