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.
| Wheeler, M D; Wehrenberg, W W; Styne, D M (1991) Growth hormone regulation by growth hormone-releasing hormone in infant rhesus monkeys. Biol Neonate 60:19-28 |
| Singh, J S; Rall, L B; Styne, D M (1991) Insulin-like growth factor I and II gene expression in Balb/C mouse liver during postnatal development. Biol Neonate 60:7-18 |
| Liu, F; Powell, D R; Styne, D M et al. (1991) Insulin-like growth factors (IGFs) and IGF-binding proteins in the developing rhesus monkey. J Clin Endocrinol Metab 72:905-11 |
| Wheeler, M D; Styne, D M (1990) Longitudinal changes in growth hormone response to growth hormone-releasing hormone in neonatal rhesus monkeys. Pediatr Res 28:15-8 |
| Wheeler, M D; Styne, D M (1988) The nonhuman primate as a model of growth hormone physiology in the human being. Endocr Rev 9:213-46 |
