 |
 Previous Article | Next Article 
The Journal of Neuroscience, April 1, 1998, 18(7):2570-2580
Distinct Ontogeny of Glucocorticoid and Mineralocorticoid
Receptor and 11 -Hydroxysteroid Dehydrogenase Types I and II mRNAs in
the Fetal Rat Brain Suggest a Complex Control of Glucocorticoid
Actions
Rochellys
Diaz,
Roger W.
Brown, and
Jonathan R.
Seckl
Molecular Medicine Centre, Western General Hospital, University of
Edinburgh, Edinburgh EH4 2XU, United Kingdom
Glucocorticoids (GCs) act via intracellular mineralocorticoid (MR)
and glucocorticoid receptors (GR). However, it has recently been
recognized that GC access to receptors is determined by the presence of
tissue-specific 11 -hydroxysteroid dehydrogenases (11-HSDs) that
catalyze the interconversion of active corticosterone and inert
11-dehydrocorticosterone. 11-HSD type 1 (11-HSD1) is a
bidirectional enzyme in vitro that acts predominantly as a reductase (regenerating corticosterone) in intact neurons. In contrast, 11-HSD type 2 (11-HSD2) is a higher affinity exclusive dehydrogenase that excludes GCs from MR in the kidney, producing aldosterone-selectivity in vivo. We have examined the
ontogeny of 11-HSD mRNAs and enzyme activity during prenatal brain
development and correlated this with GR and MR mRNA development. These
data reveal that (1) 11-HSD2 mRNA is highly expressed in all CNS
regions during midgestation, but expression is dramatically reduced
during the third trimester except in the thalamus and cerebellum; (2) 11-HSD2-like activity parallels closely the pattern of mRNA
expression; (3) 11-HSD1 mRNA is absent from the CNS until the the
third trimester, and activity is low or undectectable; and (4) GR mRNA
is highly expressed throughout the brain from midgestation, but MR gene expression is absent until the last few days of gestation. High 11-HSD2 at midgestation may protect the developing brain from activation of GR by GCs. Late in gestation, repression of 11-HSD2 gene expression may allow increasing GC activation of GR and MR, permitting key GC-dependent neuronal and glial maturational events.
Key words:
11-hydroxysteroid dehydrogenases; glucocorticoid
receptor; mineralocorticoid receptor; ontogeny; fetal brain; rats
Copyright © 1998 Society for Neuroscience 0270-6474/98/1872570-11$05.00/0
This article has been cited by other articles:
|
|
|
|
 
J. C. Geerling and A. D. Loewy
Aldosterone in the brain
Am J Physiol Renal Physiol,
September 1, 2009;
297(3):
F559 - F576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Hauser, A. Knapman, N. R. Zurcher, S. Pilloud, C. Maier, R. Diaz-Heijtz, H. Forssberg, A. Dettling, J. Feldon, and C. R. Pryce
Effects of Prenatal Dexamethasone Treatment on Physical Growth, Pituitary-Adrenal Hormones, and Performance of Motor, Motivational, and Cognitive Tasks in Juvenile and Adolescent Common Marmoset Monkeys
Endocrinology,
December 1, 2008;
149(12):
6343 - 6355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Vagnerova, Z. Vackova, P. Klusonova, F. Staud, M. Kopecky, P. Ergang, I. Miksik, and J. Pacha
Reciprocal Changes in Maternal and Fetal Metabolism of Corticosterone in Rat During Gestation
Reproductive Sciences,
November 1, 2008;
15(9):
921 - 931.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D. M Sloboda, T. J M Moss, S. Li, S. G Matthews, J. R G Challis, and J. P Newnham
Expression of glucocorticoid receptor, mineralocorticoid receptor, and 11{beta}-hydroxysteroid dehydrogenase 1 and 2 in the fetal and postnatal ovine hippocampus: ontogeny and effects of prenatal glucocorticoid exposure
J. Endocrinol.,
May 1, 2008;
197(2):
213 - 220.
[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]
|
|
|
|
|
|
|
A. Naray-Fejes-Toth and G. Fejes-Toth
Reply to Geerling and Loewy
Am J Physiol Renal Physiol,
July 1, 2007;
293(1):
F442 - F443.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Mangold and D. L. Hill
Extensive Reorganization of Primary Afferent Projections into the Gustatory Brainstem Induced by Feeding a Sodium-Restricted Diet during Development: Less Is More
J. Neurosci.,
April 25, 2007;
27(17):
4650 - 4662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Shoener, R. Baig, and K. C. Page
Prenatal exposure to dexamethasone alters hippocampal drive on hypothalamic-pituitary-adrenal axis activity in adult male rats
Am J Physiol Regulatory Integrative Comp Physiol,
May 1, 2006;
290(5):
R1366 - R1373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Holmes, C. T. Abrahamsen, K. L. French, J. M. Paterson, J. J. Mullins, and J. R. Seckl
The mother or the fetus? 11beta-hydroxysteroid dehydrogenase type 2 null mice provide evidence for direct fetal programming of behavior by endogenous glucocorticoids.
J. Neurosci.,
April 5, 2006;
26(14):
3840 - 3844.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kapoor, E. Dunn, A. Kostaki, M. H. Andrews, and S. G. Matthews
Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids
J. Physiol.,
April 1, 2006;
572(1):
31 - 44.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Keller-Wood, M. J. Powers, J. A. Gersting, N. Ali, and C. E. Wood
Genomic analysis of neuroendocrine development of fetal brain-pituitary-adrenal axis in late gestation
Physiol Genomics,
February 23, 2006;
24(3):
218 - 224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Theogaraj, C. D. John, H. C. Christian, J. F. Morris, S. F. Smith, and J. C. Buckingham
Perinatal Glucocorticoid Treatment Produces Molecular, Functional, and Morphological Changes in the Anterior Pituitary Gland of the Adult Male Rat
Endocrinology,
November 1, 2005;
146(11):
4804 - 4813.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Paterson, J. R. Seckl, and J. J. Mullins
Genetic manipulation of 11{beta}-hydroxysteroid dehydrogenases in mice
Am J Physiol Regulatory Integrative Comp Physiol,
September 1, 2005;
289(3):
R642 - R652.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M C Connell and E. Davies
The new biology of aldosterone
J. Endocrinol.,
July 1, 2005;
186(1):
1 - 20.
[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]
|
|
|
|
|
|
|
X. Wang, J. L. Pongrac, and D. B. DeFranco
Glucocorticoid Receptors in Hippocampal Neurons that Do Not Engage Proteasomes Escape from Hormone-Dependent Down-Regulation but Maintain Transactivation Activity
Mol. Endocrinol.,
September 1, 2002;
16(9):
1987 - 1998.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bertram, A. R. Trowern, N. Copin, A. A. Jackson, and C. B. Whorwood
The Maternal Diet during Pregnancy Programs Altered Expression of the Glucocorticoid Receptor and Type 2 11{beta}-Hydroxysteroid Dehydrogenase: Potential Molecular Mechanisms Underlying the Programming of Hypertension in Utero
Endocrinology,
July 1, 2001;
142(7):
2841 - 2853.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. R. Kiela, Y. S. Guner, H. Xu, J. F. Collins, and F. K. Ghishan
Age- and tissue-specific induction of NHE3 by glucocorticoids in the rat small intestine
Am J Physiol Cell Physiol,
April 1, 2000;
278(4):
C629 - C637.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-M. Ou, J. M. Storring, N. Kushwaha, and P. R. Albert
Heterodimerization of Mineralocorticoid and Glucocorticoid Receptors at a Novel Negative Response Element of the 5-HT1A Receptor Gene
J. Biol. Chem.,
April 20, 2001;
276(17):
14299 - 14307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
