MECHANISMS OF EGF ACTION IN THE FETUS AND NEONATE

Project: Research project

Project Details

Description

Hypothesis: Epidermal Growth Factor (EGF) stimulates the growth
and maturation of crucial fetal and infant tissues, actions that
could lead to new modes of therapeutic intervention to improve the
growth and development of premature human infants. Long-term Aims:
To define the effects and mechanism of action of EGF on tissue
growth and maturation in fetal and infant Rhesus monkeys, with
particular emphasis on gut and lung development, and to explore the
use of EGF for treatment of premature infants. Specific Aims: 1.
To elucidate mechanisms of action of EGF in fetal monkeys and to
differentiate the responses to amniotic fluid (oral) and systemic
(parenteral) administration of EGF in fetal Rhesus monkeys. 2. To
define the role of the adrenal axis in the mechanism of action of
EGF in fetal monkeys; from the data of the preliminary studies, we
postulate that changes in circulating adrenal hormones may mediate
some of the responses to EGF, particularly in lung. 3. To
determine if the prenatal developmental and growth responses to EGF
confer any postnatal growth advantage in prematurely delivered
Rhesus monkeys and to examine the importance of EGF in the
transition between fetal and postnatal life; we postulate that EGF
may have therapeutic applications to improve infant growth and
development, particularly in the preterm infant. Methods: EGF
will be given to fetal Rhesus monkeys via amniotic fluid (oral and
respiratory route) or intraperitoneal (systemic) administration to
determine which route is more effective. Some fetuses will receive
an adrenal enzyme blocking agent to determine the role of the fetal
adrenal gland, in particular the definitive zone, in the lung and
gut maturation already demonstrated. All fetuses will be delivered
by cesarean section at 78% of gestation; some will be used for
tissue collection while other infants will be supported in a pri-
mate neonatal intensive care unit to determine whether EGF confers
a survival advantage to the premature monkeys. Lastly, a group of
premature infants will be given only postnatal EGF to assets the
effectiveness of EGF after birth. The physiologic and biochemical
function of the lung, gut and adrenal gland will be studied, as
will their histology. EGF and TGF-alpha mRNA will be studied in
all animals to determine the control of gene expression in the
primate.
StatusFinished
Effective start/end date1/1/8912/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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