To clarify the nature of the stress hyporesponsive period that occurs in neonatal rats, the development of the response of the brain-pituitary-adrenal axis to
hypoglycemia stress in rats was assessed in vivo and in vitro. Hypothalami were removed from the brains of neonatal (9-35 days postnatal) or adult rats and incubated in vitro for sequential 30-min periods in Krebs
buffer for determination of
corticotropin-releasing factor (CRF) secretion under conditions of altered
glucose concentrations. As expected from previous studies, CRF secretion from adult hypothalami was significantly increased in severely
hypoglycemic conditions (0.55 mM
glucose) by approximately 50% above base-line values (in 5.5 mM
glucose). However, lowering
glucose did not elicit an increase in CRF release from hypothalami of rats less than 35 days of age. Hypothalami obtained from rats less than or equal to 24 days old also failed to show consistent secretory responses to
potassium depolarization. At 35 days postnatal the response to
hypoglycemia was significant and similar to the adult response. To determine if the lack of hypothalamic response to
hypoglycemia in vitro could be correlated with the in vivo responses to
hypoglycemia, rats aged 4 days to adult were injected intraperitoneally with
porcine insulin and killed at different times after injection.
Insulin injections lowered plasma
glucose levels in fasted 4-day-old rats in a dose-dependent fashion, but a nadir in
glucose (approximately 40 mg/dl) was not reached until 90 min; the same treatment produced a nadir in
glucose within 30 min in fasted rats 10 days old and older, suggesting that the 4-day-old rats are relatively
insulin insensitive.(ABSTRACT TRUNCATED AT 250 WORDS)