Gluco- and mineralocorticoid receptor-mediated regulation of neurotrophic factor gene expression in the dorsal hippocampus and the neocortex of the rat.
Gluco- and mineralocorticoid receptors (GR and MR) act via common promoter elements but may exert different effects on gene regulation in various regions of the forebrain. In order to separately analyse the role of GR and MR in the regulation of neurotrophic factor genes and their receptors, we used adrenalectomy and subsequent hormone injections in the rat as a model system. Twenty-four hours after adrenalectomy rats were injected with a single dose of corticosterone (2 and 10 mg/kg), aldosterone (0.5 mg/kg) or the synthetic glucocorticoid agonist RU 28362 (4 mg/kg). Gene expression of basic fibroblast growth factor (bFGF) and its high-affinity receptors [fibroblast growth factor receptor subtypes 1-3 (FGF-R1, FGF-R2, FGF-R3)], as well as brain-derived growth factor (BDNF) and neurotrophin-3 (NT-3) was analysed at 4 h after the hormone injection in CA1-CA4 (cornus of Ammon areas of the hippocampus) and dentate gyrus of the dorsal hippocampus and in neocortex by means of in situ hybridization. We found that bFGF is regulated in CA2, CA3 and dentate gyrus by GR and MR together, and in CA1, CA4 and neocortex by GR alone. FGF-R2 expression in the hippocampus seems to be regulated only by MR, while BDNF expression appears to depend on both receptors. FGF-R1, FGF-R3 and NT-3 were only moderately affected by the hormone activation of GR and MR acting in concert or alone in the various regions. Thus, the present findings suggest that the adrenal cortical system through GR and MR participate in the control of neurotrophic factor signalling in a highly subregion- and cellular-dependent manner.
Hansson
A C
AC
Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden; Max-Delbrück-Center for Molecular Medicine (MDC), 13125 Berlin-Buch, Germany. anita.hansson@neuro.ki.se
Cintra
A
A
Belluardo
N
N
Sommer
W
W
Bhatnagar
M
M
Bader
M
M
Ganten
D
D
Fuxe
K
K
D000315:Adrenalectomy; D000450:Aldosterone / Q000097:blood / Q000494:pharmacology*; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D019579:Neocortex / Q000737:chemistry / Q000502:physiology*; D020933:Neurotrophin 3 / Q000235:genetics; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics
D000732:Androstanols; D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D015347:RNA Probes; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D000450:Aldosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D003345:Corticosterone