Ontogeny of expression of the corticotropin-releasing factor gene in the hypothalamic paraventricular nucleus and of the proopiomelanocortin gene in rat pituitary.

The ontogeny of expression of the CRF gene in the paraventricular hypothalamic nucleus and POMC gene in the pituitary was studied in rats using in situ hybridization histochemistry and Northern blotting techniques, respectively. CRF mRNA was first detected on day 17 of gestation (E17) in the paraventricular nucleus of the hypothalamus. The levels of hypothalamic CRF mRNA increased progressively from E17 to E19-E20, decreased during the perinatal period, and increased thereafter. The levels of POMC mRNA in the pituitary paralleled the variations in hypothalamic CRF mRNA, showing a peak on E20-E21. POMC mRNA levels in the anterior pituitary were decreased on days 4-7 after birth (P4-P7) and increased steadily thereafter. In contrast to levels in the anterior pituitary, POMC mRNA levels increased steadily from P1 to P21 in the neurointermediate lobe of the pituitary. These data indicate that the expression of both the CRF and POMC genes in the paraventricular nucleus and anterior pituitary, respectively, are reduced during the first week of life, i.e. within the so-called stress nonresponsive period. Our observations suggest that an impaired regulation of ACTH and CRF synthesis due to an immature neuronal pathway within the brain or increased glucocorticoid feedback may account for the stress nonresponsive period.