The purpose of this proposal is to identify the changing neural substrates which mediate the neuroendocrine response to stress during ontogeny in rats. We will test the specific hypothesis that inhibition of growth hormone secretion changes from neural mechanisms independent of corticotropin releasing factor (CRF) to a process dependent on CRF during the first three postnatal weeks. This hypothesis will be tested by using three different strategies. First the ontogeny of growth hormone, ACTH, corticosterone and prolactin responses to distinct stressor (ether, immobilization, maternal deprivation) will be established from postnatal day 21 to puberty. Second, the ability of CRF to elicit a pattern of sympathetic and pituitary activation will be assessed by determining heart rate, blood glucose, ACTH, growth hormone, prolactin, and corticosterone after peripheral and central CRF administration. Third, the ability of the CRF antagonist alpha helical CRF or immunoeutralization of released CRF to prevent growth hormone responses to stress will be tested from postnatal day 1-20. The fourth and final goal will be to investigate the hypothesis that endogenous opioids mediate stress-induced hormone secretion early in ontogeny, before CRF assumes this role. This hypothesis will be tested by evaluating the ability of opiate antagonists with high potency for mu or kappa opiate receptors to prevent stress-induced inhibition of growth hormone secretion and stimulation of HPA function early in ontogeny. These studies should provide important insight into how this sequence of neuronal development organize age-characteristic responses to stress, and permits appropriate physiologic adaptation of the developing organism to its environment. Furthermore, by understanding the ontogeny of different components of the stress response and its neural mediators, the impact of early stress on subsequent neuroendocrine reactivity and behavioral development can be better understood.
| Eck, J B; Kuhn, C M (1992) Effect of ether stress on growth hormone during development in the neonatal rat. Neuroendocrinology 56:605-10 |
| Borowsky, B; Kuhn, C M (1992) D1 and D2 dopamine receptors stimulate hypothalamo-pituitary-adrenal activity in rats. Neuropharmacology 31:671-8 |
| Kuhn, C; Albright, K; Francis, R (1991) Corticotropin releasing factor stimulates growth hormone secretion in neonatal rats. Life Sci 49:1427-34 |
