# REGULATION OF FETAL HEPATIC GROWTH

> **NIH NIH R01** · RHODE ISLAND HOSPITAL · 1994 · $138,139

## Abstract

This application is for continuation of a project aimed at investigating
the mechanisms leading to decreased hepatic growth in rat fetuses with
intrauterine growth retardation (IUGR).  It focuses on fundamental
differences in growth regulation between fetal and adult hepatocytes in
primary culture.  The proposed studies are based on several key findings
which came out of the first cycle of this grant: [1] Cultured fetal rat
hepatocytes, in contract to cultured adult rat hepatocytes, exhibit
autocrine growth stimulation; [2] Fetal hepatocytes display constitutive
expression of the proto-oncogene, c-myc; [3] Insulin and Transforming
Growth Factor-alpha (TGF-alpha) potentiate the DNA synthesis of
hepatocytes above basal levels in a dose-responsive manner while TGF-beta
inhibits fetal hepatocyte growth; [4] Insulin potentiation of DNA
synthesis is abolished in hepatocytes from growth retarded fetuses.
Based on these findings, we have formulated the following corresponding
specific aims: [1] Study the ontogeny of three signal transducing protein
kinases (Protein Kinase C[PK-C}, Mitogen Activated Protein Kinases [MAP
Kinases] and casein Kinase II [CS-II] which are involved in mitogen
activation of growth.  Determinations will be made in adult liver, fetal
liver (days 17 through 21 of gestation), cultured adult hepatocytes and
cultured fetal hepatocytes; [2] Determine the fetal hepatocyte
transcription rates for exons I, II and III of c-myc, thereby focusing
on the phenomenon of "pausing" which has a critical effect on c-myc
transcription.  Comparisons will be made with adult rat hepatocytes in
primary culture; [3] Determine the effect of insulin, TGF-alpha and TGF-
beta on signal transducing kinase activities and c-myc transcriptional
regulation (initiation and elongation) in cultures of fetal rat
hepatocytes.  Comparisons will be made using cultures of adult rat
hepatocytes; [4] Do comparative studies using hepatocytes from control
IUGR fetuses to determine the response of signal transducing protein
kinases and c-myc regulation to insulin as well as to the transforming
growth factors.,  It is anticipated that the results of these studies
will shed light on basic mechanisms regulating hepatic growth in the
fetus and the nature of perturbations in these mechanisms which accompany
IUGR.

## Key facts

- **NIH application ID:** 2199178
- **Project number:** 5R01HD024455-06
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **SAM.gov UEI:** N876TLXYGCG4
- **Principal Investigator:** Philip A. Gruppuso
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $138,139
- **Award type:** 5
- **Project period:** 1989-04-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199178

## Citation

> US National Institutes of Health, RePORTER application 2199178, REGULATION OF FETAL HEPATIC GROWTH (5R01HD024455-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199178. Licensed CC0.

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