11 beta-hydroxysteroid dehydrogenase bioactivity and messenger RNA expression in rat forebrain: localization in hypothalamus, hippocampus, and cortex. 1990

M P Moisan, and J R Seckl, and C R Edwards
University of Edinburgh, Department of Medicine, Western General Hospital, UK.

In peripheral aldosterone target sites (e.g., kidney), 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) metabolizes corticosterone to inactive 11-dehydrocorticosterone and thus protects mineralocorticoid receptors from exposure to corticosterone in vivo. We have investigated whether 11 beta-OHSD could account for the site-specific differences in corticosteroid receptor sensitivity to corticosterone in rat brain. Enzyme activity, estimated as the percentage conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone in the presence of NADP+ (200 microM), was: hippocampus, 55.8 +/- 2.7%; cortex, 52 +/- 3.1%; pituitary; 40 +/- 2%, hypothalamus, 26.1 +/- 1.2%; brain stem, 21.4 +/- 1.7%; and spinal cord, 12.3 +/- 1.8%. Northern blots, using [32P]dCTP-labeled probes from an 11 beta-OHSD cDNA clone derived from rat liver, showed expression of a single mRNA species in all brain areas, of identical size to 11 beta-OHSD mRNA in liver and kidney. Highest expression was found in hippocampus and cortex. In situ hybridization, using [35S]UTP-labeled cRNA probes, localized high mRNA expression to cerebral cortex (particularly parietal cortex, layer IV), hippocampus (highest in CA3), hypothalamic medial preoptic area and arcuate nuclei and anterior pituitary. In conclusion, there is localized 11 beta-OHSD mRNA expression and enzyme bioactivity in rat brain. The distribution of 11 beta-OHSD corresponds to areas of reduced glucocorticoid or mineralocorticoid receptor affinity for corticosterone. Therefore, 11 beta-OHSD may regulate the access of corticosterone to cerebral mineralocorticoid and/or glucocorticoid receptors and thus modulate corticosteroid effects on brain function.

UI MeSH Term Description Entries
D007031 Hypothalamus Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE. Lamina Terminalis,Preoptico-Hypothalamic Area,Area, Preoptico-Hypothalamic,Areas, Preoptico-Hypothalamic,Preoptico Hypothalamic Area,Preoptico-Hypothalamic Areas
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009693 Nucleic Acid Hybridization Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503) Genomic Hybridization,Acid Hybridization, Nucleic,Acid Hybridizations, Nucleic,Genomic Hybridizations,Hybridization, Genomic,Hybridization, Nucleic Acid,Hybridizations, Genomic,Hybridizations, Nucleic Acid,Nucleic Acid Hybridizations
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D003345 Corticosterone An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)

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