Dynamic changes in glucocorticoid and mineralocorticoid receptor mRNA in the developing guinea pig brain

Abstract

The guinea pig has a high degree of neurological maturity at birth. Since glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) are central to several aspects of brain and neuroendocrine development, we examined the hypothesis that development of central GR and MR systems takes place during fetal life, in species which give birth to mature 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 followed by computerized image analysis. MR mRNA was confined to limbic structures, and was present at high levels in the hippocampus and dentate gyrus by gd40. Hippocampal MR mRNA levels decreased with the progression 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, GR mRNA levels increased with progression of gestation, attaining highest levels near term. In contrast to the hippocampus, GR mRNA levels were highest in the PVN at gd40–45, but decreased dramatically in the last 25 days of gestation. In conclusion, there are dynamic site-specific changes in the expression of corticosteroid receptors in the brain of the fetal guinea pig, at the time of most rapid brain growth. The decreases in GR mRNA levels in the PVN in late gestation likely facilitate the simultaneous increases in ACTH and cortisol that occur near term, and which are critical for the delivery of viable young.