# THE HORMONAL CONTROL OF FETAL GROWTH

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 1994 · $190,387

## Abstract

This proposal is based on the hypothesis that the Insulin-like Growth
Factors (IGF-I and IGF-II) are essential to the regulation of embryonic and
fetal growth and development.  We postulate that the IGFs, IGF receptors,
and IGF binding proteins (IGFBPs) are expressed from early in
embryogenesis, and that the time of onset and control of expression of
these proteins differs depending on the stage of cellular maturation.
Furthermore, because the IGFs have diverse biologic effects, we believe
that all IGF in utero actions have not been defined.  The goals of this
proposal therefore, are to determine the time of inset of IGF, IGF receptor
and IGFBP expression; to elucidate the factors that regulate IGFs in utero;
and to define IGF actions and mechanisms of action important to
development.  Specifically, we will determine the ontogeny and sites of
expression of the IGFs, IGF receptors and IGFBPs from pre-implantation
embryogenesis through neonatal life in rats and mice (Spec. Aim 1).  To
define the regulation IGF, IGF receptor and IGFBP expression during in
utero and neonatal development (Spec. Aim 2), we will assess the factors
that modulate in vitro expression in embryonal carcinoma cell lines and in
cultured fetal and neonatal rat fibroblasts.  We also will evaluate in vivo
expression of IGFs, IGF receptors and IGFBPs in tissues of fetal rats
subjected to perturbations that result in intrauterine growth retardation
and to the administration of substances found to alter the expression of
these proteins in vitro.  To determine the factors that stimulate IGF
transcription (Spec. Aim 3), we will study the regulation of expression of
fusion genes linking IGF 5' genomic flanking elements to reporter genes in
stably transfected cultured cells and transgenic mice.  Using a number of
transgenes designed to alter IGF expression, we will study in utero actions
and mechanisms of action of IGFs in cultured stably transfected cells
(Spec. Aim 4) and transgenic mice (Spec. aim 5).  To investigate IGF
actions, we will:  a) create IGF-I expression in embryonic and fetal-
derived cells that do not normally express IGF-I using transgenes that fuse
either the metallothionein promoter or the mIGF-II genomic 5' flanking
region to an IGF-IA gene, b) generate in utero IGF-I overexpression in
transgenic mice using the fusion of MIGF-II 5' flanking IGFs and in
transgenic mice using fusion genes that express anti-sense IGF transcripts
or ribozymes that specifically cleave IGF transcripts.  To examine the
mechanisms of IGF-I's actions, we will:  a) examine changes in the
expression of IGF receptors and IGFBPs as a consequence of each of the
above alterations in IGF expression, b) test IGF-I's potential autocrine
actions, using transgenes expressing mutant IGF-I molecules that are not
secreted either because they have amino acid (KDEL) trailer sequence
targeting the endoplasmic reticulum or because they lack a signal peptide,
and c) determine the effect of IGFBP-1 expression o...

## Key facts

- **NIH application ID:** 2196581
- **Project number:** 5R01HD008299-21
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **SAM.gov UEI:** D3LHU66KBLD5
- **Principal Investigator:** AUGUSTINE JOSEPH D'ERCOLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $190,387
- **Award type:** 5
- **Project period:** 1977-06-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196581

## Citation

> US National Institutes of Health, RePORTER application 2196581, THE HORMONAL CONTROL OF FETAL GROWTH (5R01HD008299-21). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196581. Licensed CC0.

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