DYNAMIC CHANGES IN GLUCOCORTICOID AND MINERALOCORTICOID RECEPTOR MESSENGER-RNA IN THE DEVELOPING GUINEA-PIG BRAIN

The guinea pig has a high degree of neurological maturity at birth. Si nce glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) are central to several aspects of brain and neuroendocrine developmen t, we examined the hypothesis that development of central GR and MR sy stems takes place during fetal life, in species which give birth to ma ture young. Fetal guinea pigs were retrieved on gestational days (gd) 40-45, 50-55, 60-65. A group of 7-day old neonates was also euthanized . Levels of GR and MR mRNA were determined by in situ hybridization fo llowed by computerized image analysis. MR mRNA was confined to Limbic structures, and was present at high levels in the hippocampus and dent ate gyrus by gd40. Hippocampal MR mRNA levels decreased with the progr ession of gestation. GR mRNA was more widely distributed, with highest levels being expressed in the cingulate cortex, hippocampus, amygdala and hypothalamic paraventricular nucleus (PVN). In the hippocampus, G R mRNA levels increased with progression of gestation, attaining highe st levels near term. In contrast to the hippocampus, GR mRNA levels we re highest in the PVN at gd40-45, but decreased dramatically in the la st 25 days of gestation. In conclusion, there are dynamic site-specifi c changes in the expression of corticosteroid receptors in the brain o f the fetal guinea pig, at the time of most rapid brain growth. The de creases in GR mRNA levels in the PVN in late gestation likely facilita te the simultaneous increases in ACTH and cortisol that occur near ter m, and which are critical for the delivery of viable young. (C) 1998 E lsevier Science B.V.