Ontogeny of the β-Endorphin Response to Stress in the Rat: Role of the Pituitary and the Hypothalamus

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Abstract
Neonatal rats show a period of diminished adrenocorticotropin responsiveness to stress during the first 2 weeks of life. To test whether β-endorphin-like peptides (β-EPLPs) follow the same pattern of hyporesponsiveness to stress during this period, we examined the ontogeny of the β-EPLPs response to two different types of stressors (ether vapors and cold) during the early postnatal period. The content of β-EPLPs was estimated in the serum, the pituitary gland and the hypothalamus prior to and 5 min following exposure to stressful stimuli. Furthermore, to determine the relationship between the responsiveness of β-EPLPs to stress and that of the hypothalamic-pituitary-adrenal axis in the developing rat, the content of hypothalamic corticotropin-releasing factor (CRF) and serum corticosterone was estimated prior to and following stress. Results indicated that stress induced an increase in the serum corticosterone levels at all ages tested (days 1–22), however, the stress-induced elevations of serum corticosterone were significantly greater on days 1 and 22 than on days 3–14. Significant stress-induced elevations of serum immunoreactive β-endor-phin (ir-β-EP) were observed on days 14 and 22 of life, while changes on days 1, 3, 8 and 10 were either nonexistent or not statistically significant. Gel filtration analysis revealed that the increases in serum ir-β-EP following stress on days 14 and 22 resulted primarily from increases in the β-lipotropin component with lesser increases in the β-endorphin component. Pituitary content of β-EPLPs was not affected by stress before day 10, but was markedly reduced in the 10- and 14-day-old rats, following stress. A similar, although not statistically significant decrease was observed in the pituitary content of β-EPLPs of the 22-day-old rats after exposure to stress. Furthermore, exposure to cold stress in the 14-day-old rats induced more pronounced changes in the serum ir-β-EP and corticosterone levels as well as in the pituitary ir-β-EP content than it did with ether stress. Despite variations in serum corticosterone as well as serum and pituitary content of β-EPLPs, no changes in the hypothalamic ir-β-EP content were seen in rats after subjection to stress, while small, not statistically significant reductions in the hypothalamic CRF content were observed at 5 min after the onset of stress in the 14- and 22-day-old rats. Thus, during the first 2 weeks of life neonatal rats exhibit a reduced capacity to secrete β-EPLPs in response to stress. This period of reduced responsiveness of the β-EP system to stress coincides with the previously demonstrated stress hyporesponsive period of the hypothalamic-pituitary-adrenal axis.