Sexually dimorphic effects of maternal adrenalectomy on hypothalamic corticotrophin-releasing factor, glucocorticoid receptor and anterior pituitary POMC mRNA levels in rat neonates

The stress hyporesponsive period (SHRP) occurs during the first two weeks of life (from day 4 to day 14) in the rat. SHRP may occur due to immature hypothalamic-pituitary-adrenal (HPA) regulatory mechanisms of the neonate. Decreased expression of corticotropin-releasing factor (CRF) has been observed during this period, and this decreased hypothalamic 'drive' may contribute to the manifestation of SHRP in the rat neonate. Since maternal corticosteroids are elevated toward the end of gestation they may suppress fetal CRF expression leading to a less than adequate activation of the neonatal hypothalamus in response to stress. Therefore, the purpose of the present study was to clarify the contribution of maternal glucocorticoids to the decreased CRF expression observed during SHRP in the neonatal rat. We investigated the effects of maternal adrenalectomy on hypothalamic CRF, glucocorticoid receptor (GR) and anterior pituitary proopiomelanocortin (POMC) mRNA levels in male and female neonates. Maternal adrenalectomy, or sham surgery, was performed on day 8 of gestation and the mRNA levels of CRF, GR and POMC were measured by Northern blotting in the offspring on their postnatal days 1, 7, 14, and 21. The observed changes in the mRNA levels of these genes suggests that an important developmental event occurs in the regulation of these HPA genes between neonatal days 7 and 14 corresponding to the termination of SHRP. Female offspring had significantly higher levels of CRF mRNA than males throughout this period. The lack of maternal corticosteroids evoked a gender-specific response in the neonates. In female offspring, maternal adrenalectomy resulted in a dramatic and correlated increase in mRNA levels of hypothalamic CRF and GR on day 14, with pituitary POMC expression not following this increase. There was no significant effect of maternal adrenalectomy on the expression of these genes in males. These results suggest a sex difference in response to maternal glucocorticoids in the fetus. However, the role of maternal corticosteroids in the low expression of CRF during SHRP could not be established from this study, since their removal by adrenalectomy did not advance the expression profile of CRF toward an earlier increase in the neonatal hypothalamus.