PRENATAL DEVELOPMENT OF GLUCOCORTICOID RECEPTOR GENE-EXPRESSION AND IMMUNOREACTIVITY IN THE RAT-BRAIN AND PITUITARY-GLAND - A COMBINED IN-SITU HYBRIDIZATION AND IMMUNOCYTOCHEMICAL ANALYSIS

By means of in situ hybridization and immunocytochemical techniques it has been possible to follow the prenatal development of glucocorticoi d receptor (GR) messenger RNA (mRNA) expression and GR immunoreactivit y (IR) in the rat brain from embryonic day (E) 15 to 22. A 700-base-pa ir GR cDNA fragment was used for RNA probe generation. In the immunocy tochemical analysis a mouse monoclonal antibody (IgG2a) against the ra t liver GR was used in combination with the indirect fluorescence tech nique or the avidin-biotin immunoperoxidase, method. At E15 till E22 a moderate to strong GR mRNA signal was observed within the neuro-epith elium from the medulla oblongata to the telencephalon, A moderate to s trong labelling was also present within the paraventricular hypothalam ic nucleus, the arcuate nucleus, the nucleus raphe magnus, the nucleus raphe obscurus and the locus coeruleus. In these areas a weak to mode rate nuclear GR IR developed in nerve cells 1 or 2 days after the appe arance of the GR mRNA signal. From E15 the adenohypophysis showed the strongest expression of GR mRNA. At E17 a strong GR IR was especially demonstrated in the nuclei of many pituitary cells, some exhibiting ad renocorticotropin IR. The results open up the possibility that there e xist active GR in embryonic life capable of regulating proliferation e vents within the adenohypophysis and the neuro-epithelia of the brain. This embryonic GR may modulate the development of inter alia neuroend ocrine areas such as the paraventricular and arcuate nuclei and arousa l-related areas such as the central 5-hydroxytryptamine and noradrenal ine neuronal systems. Provided that this embryonic GR is capable of be coming activated by glucocorticoids in fetal life, it may mediate seve ral neurochemical and behavioural impairments caused by prenatal stres s.