| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Endocrinology, Vol 127, 1450-1455, Copyright © 1990 by Endocrine Society
ARTICLES |
MP Moisan, JR Seckl and CR 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.
This article has been cited by other articles:
 |
|
 |
|
  A. Balachandran, H. Guan, M. Sellan, S. van Uum, and K. Yang Insulin and Dexamethasone Dynamically Regulate Adipocyte 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Endocrinology, August 1, 2008; 149(8): 4069 - 4079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. Gomez-Sanchez, D. G. Romero, A. F. de Rodriguez, M. P. Warden, Z. Krozowski, and C. E. Gomez-Sanchez Hexose-6-Phosphate Dehydrogenase and 11{beta}-Hydroxysteroid Dehydrogenase-1 Tissue Distribution in the Rat Endocrinology, February 1, 2008; 149(2): 525 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. W. Yau, K. M. McNair, J. Noble, D. Brownstein, C. Hibberd, N. Morton, J. J. Mullins, R. G. M. Morris, S. Cobb, and J. R. Seckl Enhanced Hippocampal Long-Term Potentiation and Spatial Learning in Aged 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Knock-Out Mice J. Neurosci., September 26, 2007; 27(39): 10487 - 10496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Buren, S.-A. Bergstrom, E. Loh, I. Soderstrom, T. Olsson, and C. Mattsson Hippocampal 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Messenger Ribonucleic Acid Expression Has a Diurnal Variability that Is Lost in the Obese Zucker Rat Endocrinology, June 1, 2007; 148(6): 2716 - 2722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Paterson, M. C. Holmes, C. J. Kenyon, R. Carter, J. J. Mullins, and J. R. Seckl Liver-Selective Transgene Rescue of Hypothalamic-Pituitary-Adrenal Axis Dysfunction in 11{beta}-Hydroxysteroid Dehydrogenase Type 1-Deficient Mice Endocrinology, March 1, 2007; 148(3): 961 - 966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. W. Yau, J. Noble, M. Graham, and J. R. Seckl Central Administration of a Cytochrome P450-7B Product 7{alpha}-Hydroxypregnenolone Improves Spatial Memory Retention in Cognitively Impaired Aged Rats J. Neurosci., October 25, 2006; 26(43): 11034 - 11040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. S. Densmore, N. M. Morton, J. J. Mullins, and J. R. Seckl 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Induction in the Arcuate Nucleus by High-Fat Feeding: A Novel Constraint to Hyperphagia? Endocrinology, September 1, 2006; 147(9): 4486 - 4495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Kershaw, N. M. Morton, H. Dhillon, L. Ramage, J. R. Seckl, and J. S. Flier Adipocyte-Specific Glucocorticoid Inactivation Protects Against Diet-Induced Obesity Diabetes, April 1, 2005; 54(4): 1023 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Tomlinson, E. A. Walker, I. J. Bujalska, N. Draper, G. G. Lavery, M. S. Cooper, M. Hewison, and P. M. Stewart 11{beta}-Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response Endocr. Rev., October 1, 2004; 25(5): 831 - 866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Sandeep, J. L. W. Yau, A. M. J. MacLullich, J. Noble, I. J. Deary, B. R. Walker, and J. R. Seckl From The Cover: 11{beta}-Hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics PNAS, April 27, 2004; 101(17): 6734 - 6739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Seckl, N. M. Morton, K. E. Chapman, and B. R. Walker Glucocorticoids and 11beta-Hydroxysteroid Dehydrogenase in Adipose Tissue Recent Prog. Horm. Res., January 1, 2004; 59(1): 359 - 393. [Abstract] [Full Text]
|
|
|
|
|
|
C. Mattsson, M. Lai, J. Noble, E. McKinney, J. L. Yau, J. R. Seckl, and B. R. Walker Obese Zucker Rats Have Reduced Mineralocorticoid Receptor and 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression in Hippocampus--Implications for Dysregulation of the Hypothalamic-Pituitary-Adrenal Axis in Obesity Endocrinology, July 1, 2003; 144(7): 2997 - 3003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Grottoli, R. Giordano, B. Maccagno, M. Pellegrino, E. Ghigo, and E. Arvat The Stimulatory Effect of Canrenoate, a Mineralocorticoid Antagonist, on the Activity of the Hypothalamus-Pituitary-Adrenal Axis Is Abolished by Alprazolam, a Benzodiazepine, in Humans J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4616 - 4620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Seckl and B. R. Walker Minireview: 11{beta}-Hydroxysteroid Dehydrogenase Type 1-- A Tissue-Specific Amplifier of Glucocorticoid Action Endocrinology, April 1, 2001; 142(4): 1371 - 1376. [Abstract] [Full Text]
|
|
|
|
|
|
J. L. W. Yau, J. Noble, C. J. Kenyon, C. Hibberd, Y. Kotelevtsev, J. J. Mullins, and J. R. Seckl Lack of tissue glucocorticoid reactivation in 11beta -hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments PNAS, March 22, 2001; (2001) 71562698. [Abstract] [Full Text]
|
|
|
|
|
|
H. J. Harris, Y. Kotelevtsev, J. J. Mullins, J. R. Seckl, and M. C. Holmes Intracellular Regeneration of Glucocorticoids by 11{beta}-Hydroxysteroid Dehydrogenase (11{beta}-HSD)-1 Plays a Key Role in Regulation of the Hypothalamic-Pituitary-Adrenal Axis: Analysis of 11{beta}-HSD-1-Deficient Mice Endocrinology, January 1, 2001; 142(1): 114 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Mensah-Nyagan, J.-L. Do-Rego, D. Beaujean, V. Luu-The, G. Pelletier, and H. Vaudry Neurosteroids: Expression of Steroidogenic Enzymes and Regulation of Steroid Biosynthesis in the Central Nervous System Pharmacol. Rev., March 1, 1999; 51(1): 63 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Vazquez, J. F. Lopez, M. I. Morano, S. P. Kwak, S. J. Watson, and H. Akil {alpha}, {beta}, and {gamma} Mineralocorticoid Receptor Messenger Ribonucleic Acid Splice Variants: Differential Expression and Rapid Regulation in the Developing Hippocampus Endocrinology, July 1, 1998; 139(7): 3165 - 3177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. de Kloet, E. Vreugdenhil, M. S. Oitzl, and M. Joëls Brain Corticosteroid Receptor Balance in Health and Disease Endocr. Rev., June 1, 1998; 19(3): 269 - 301. [Abstract] [Full Text]
|
|
|
|
|
|
R. Diaz, R. W. Brown, and J. R. Seckl Distinct Ontogeny of Glucocorticoid and Mineralocorticoid Receptor and 11beta -Hydroxysteroid Dehydrogenase Types I and II mRNAs in the Fetal Rat Brain Suggest a Complex Control of Glucocorticoid Actions J. Neurosci., April 1, 1998; 18(7): 2570 - 2580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kotelevtsev, M. C. Holmes, A. Burchell, P. M. Houston, D. Schmoll, P. Jamieson, R. Best, R. Brown, C. R. W. Edwards, J. R. Seckl, et al. 11beta -Hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress PNAS, December 23, 1997; 94(26): 14924 - 14929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. White, T. Mune, and A. K. Agarwal 11{beta}-Hydroxysteroid Dehydrogenase and the Syndrome of Apparent Mineralocorticoid Excess Endocr. Rev., February 1, 1997; 18(1): 135 - 156. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. W. Souness and D. J. Morris 11{alpha}- and 11ß-Hydroxyprogesterone, Potent Inhibitors of 11ß-Hydroxysteroid Dehydrogenase, Possess Hypertensinogenic Activity in the Rat Hypertension, March 1, 1996; 27(3): 421 - 425. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Lombes, N. Alfaidy, E. Eugene, A. Lessana, N. Farman, and J.-P. Bonvalet Prerequisite for Cardiac Aldosterone Action : Mineralocorticoid Receptor and 11ß-Hydroxysteroid Dehydrogenase in the Human Heart Circulation, July 15, 1995; 92(2): 175 - 182. [Abstract] [Full Text]
|
|
|
|
|
|
J. L. W. Yau, J. Noble, C. J. Kenyon, C. Hibberd, Y. Kotelevtsev, J. J. Mullins, and J. R. Seckl Lack of tissue glucocorticoid reactivation in 11beta -hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments PNAS, April 10, 2001; 98(8): 4716 - 4721. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
