THE CONTROL OF GROWTH FACTORS

Project: Research project

Description

These studies will define the role of growth hormone releasing
factor (GHRH) and growth hormone release inhibitory factor
(SRIF) in the control of growth hormone (GH) secretion in the
neonatal monkey as a model of human development. Rhesus
monkeys have similar endocrine characteristics to human beings
and allow the detailed study of endocrine interaction under
controlled conditions which are ethically impossible to achieve
in human beings. A primate model of growth hormone deficiency
would allow study of diagnostic and therapeutic techniques
which may be of benefit in children with growth hormone
deficiency, a disease which can cause, besides poor growth,
severe hypoglycemia and its neurological sequella. The proposed sequence of events to be studied are: (1) newborn
primates have elevated plasma GH levels due to immaturity of
the hypothalamic-pituitary axis, leading to a decreased SRIF to
GHRH ratio; (2) the decrease in GH by 6 days after birth is
due to a progressive increase in the SRIF/GHRH ratio; (3) lower
plasma IGF I values in the newborn than in the adult are due to
inadequate stimulation of IGF I production by GH due to a)
decreased GH secretion or b) inadequate GH receptor number. Studies will be performed in animals that have chronically
placed IV catheters terminating either in a subcutaneous port
(newborns) or threaded through a protective metal cable
attached to a swivel outside the cage (several months of age).
The neonate can then cling to the chair adapted mother with
hands restrained, and the subcultaneous. Thus, mother and
child will spend all but a few hours in their cages. The
several month old monkey can be free within its cage and
sampling accomplished through the catheter without
disturbance. GHRH, SRIF and antisera to both (to neutralize
GHRH or SRIF before they reach pituitary receptors) will be
given intravenously by bolus or continuously by osmotic
minipumps and the resulting effects in plasma GH, SRIF, IGF I
and IGF II determined. These studies are designed to establish the neonatal primate
model as a useful method of testing diagnostic and therapeutic
regimens for human neonatal hypopituitarism. The ultimate goal
is to define the biological role of GH and the somatomedins in
human fetal and neonatal development.
StatusFinished
Effective start/end date7/1/866/30/89

Funding

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

Fingerprint

Growth Hormone
Intercellular Signaling Peptides and Proteins
Newborn Infant
Insulin-Like Growth Factor I
Haplorhini
Catheters
Mothers
Somatotropin Receptors
Hypopituitarism
Insulin-Like Growth Factor II
Human Development
Somatomedins
Growth
Fetal Development
Hypoglycemia
Primates
Immune Sera
Metals
Parturition

ASJC

  • Medicine(all)