Long-term failure of compensatory growth in rats following acute neonatal passive immunization against growth hormone-releasing hormone

Interruption of hypothalamic growth hormone-releasing hormone (GHRH) secretion by administration of antiserum against GHRH (GHRH-ab) decreases growth hormone (GH) secretion and inhibits growth in rats. The present study was undertaken to investigate whether there is a period of accelerated or catch-up growth following a period of growth arrest induced by GHRH-ab treatment. Neonatal male and female rats were injected daily on days 1-14 of age. Animals received normal rabbit serum (NRS) or GHRH-ab subcutaneously at a dose of 5 mul/10 g body weight. Body weight, serving as an index of somatic growth, was monitored over the next 3 months. The increase in absolute body weight and growth velocity of GHRH-ab-treated rats, regardless of gender, was lower than the increase of NRS-treated animals. Significant decreases were observed by day 13 of age in the female rats and day 17 in the male rats. The percent differences and absolute difference in weight between the two treatment groups clearly demonstrated that the GHRH-ab-treated rats did not demonstrate any period of catch-up growth. A second group of animals was treated in a similar fashion to evaluate serum GH concentrations at three months of age. Pulsatile GH secretion, as assessed by peak frequency and amplitude, was normal in all of the rats, suggesting that the failure of catch-up growth in the GHRH-ab-treated animals was not due to decreased GH secretion. The failure of catch-up growth following transient growth arrest induced by GHRH deprivation suggests that a functional GHRH/GH neuroendocrine system is critical during the neonatal period to establish normal growth of the animal on a long-term basis.