Prenatal development of glucocorticoid receptor gene expression and immunoreactivity in the rat brain and pituitary gland: A combined in situ hybridization and immunocytochemical analysis

Antonio Cintra, Valentina Solfrini, Bernd Bunnemann, Sam Okret, Francesca Borlolotti, Jan-Ake Gustafsson, Kjell Fuxe

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

By means of in situ hybridization and immunocytochemical techniques it has been possible to follow the prenatal development of glucocorticoid receptor (GR) messenger RNA (mRNA) expression and GR immunoreactivity (IR) in the rat brain from embryonic day (E) 15 to 22. A 700-base-pair GR cDNA fragment was used for RNA probe generation. In the immunocytochemical analysis a mouse monoclonal antibody (IgG2a) against the rat liver GR was used in combination with the indirect fluorescence technique or the avidin-biotin immunoperoxidase method. At E15 till E22 a moderate to strong GR mRNA signal was observed within the neuro-epithelium from the medulla oblongata to the telencephalon. A moderate to strong labelling was also present within the paraventricular hypothalamic nucleus, the arcuate nucleus, the nucleus raphe magnus, the nucleus raphe obscurus and the locus coeruleus. In these areas a weak to moderate nuclear GR IR developed in nerve cells 1 or 2 days after the appearance 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 adrenocorticotropin IR. The results open up the possibility that there exist active GR in embryonic life capable of regulating proliferation events within the adenohypophysis and the neuro-epithelia of the brain. This embryonic GR may modulate the development of inter alia neuroendocrine areas such as the paraventricular and arcuate nuclei and arousal-related areas such as the central 5-hydroxytryptamine and noradrenaline neuronal systems. Provided that this embryonic GR is capable of becoming activated by glucocorticoids in fetal life, it may mediate several neurochemical and behavioural impairments caused by prenatal stress.

Original languageEnglish (US)
Pages (from-to)1133-1147
Number of pages15
JournalNeuroendocrinology
Volume57
Issue number6
DOIs
StatePublished - Jan 1 1993

Keywords

  • Adenohypophysis
  • Adrenocorticotropin
  • Brain
  • Glucocorticoid receptor
  • Glucocorticoid receptor mRNA
  • Immunoreactivity
  • In situ hybridization
  • Locus coeruleus
  • Neuro-epithelium
  • Raphe
  • Rat

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)

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