Main |
Browse Volumes |
Forthcoming Volumes |
Annals PrePrints |
Annals Extra |
E-mail Alerts |
Subscriptions & Orders |
New Proposals |
Author Guidelines |
About Annals |
Help |
 |
|
|
|
|
|
Glucocorticoid Programming
JONATHAN R. SECKL AND
MICHAEL J. MEANEY
Endocrinology Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK
Douglas Hospital Research Center, McGill Program for the Study of Behavior, Genes & Environment, Department of Psychiatry, Verdun H4H 1R3, Canada
Address for correspondence: Professor Jonathan Seckl, Edinburgh University, Molecular Medicine Centre, Western General Hospital, Edinburgh, EH4 2XU, UK. Voice: (44) 131-651-1035; fax: (44) 131-651-1085. J.Seckl{at}ed.ac.uk
Epidemiological evidence suggests that an adverse fetal environment permanently programs physiology, leading to increased risks of cardiovascular, metabolic, and neuroendocrine disorders in adulthood. Prenatal glucocorticoid excess or stress might link fetal maturation and adult pathophysiology. In a variety of animal models, prenatal glucocorticoid exposure or inhibition of 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), the fetoplacental "barrier" to maternal glucocorticoids, reduces birth weight and causes permanent hypertension, hyperglycemia, and increased hypothalamic-pituitary-adrenal axis (HPA) activity and behavior resembling anxiety. In humans, 11ß-HSD2 gene mutations cause low birth weight and reduced placental 11ß-HSD2 activity associated with intrauterine growth retardation. Low birth weight babies have higher plasma cortisol levels throughout adult life, indicating HPA programming. The molecular mechanisms may reflect permanent changes in the expression of specific transcription factors; key is the glucocorticoid receptor itself. Differential programming of the glucocorticoid receptor in different tissues reflects effects upon one or more of the multiple tissue-specific alternate first exons/promoters of the glucocorticoid receptor gene. Overall, the data suggest that either pharmacological or physiological exposure to excess glucocorticoids prenatally programs pathologies in adult life.
Key Words: glucocorticoids • programming • birth weight • 11ß-HSD-2
This article has been cited by other articles:
|
|
|
|
 
P. D. Gluckman, M. A. Hanson, C. Cooper, and K. L. Thornburg
Effect of In Utero and Early-Life Conditions on Adult Health and Disease
N. Engl. J. Med.,
July 3, 2008;
359(1):
61 - 73.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. E. Michael and A. T. Papageorghiou
Potential significance of physiological and pharmacological glucocorticoids in early pregnancy
Hum. Reprod. Update,
June 13, 2008;
(2008)
dmn021v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Farmer, A. Korszun, M. J. Owen, N. Craddock, L. Jones, I. Jones, J. Gray, R. J. Williamson, and P. McGuffin
Medical disorders in people with recurrent depression
The British Journal of Psychiatry,
May 1, 2008;
192(5):
351 - 355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Raikkonen, A.-K. Pesonen, K. Heinonen, E. Kajantie, P. Hovi, A.-L. Jarvenpaa, J. G. Eriksson, and S. Andersson
Depression in Young Adults With Very Low Birth Weight: The Helsinki Study of Very Low-Birth-Weight Adults
Arch Gen Psychiatry,
March 1, 2008;
65(3):
290 - 296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. W. H. Rumball, M. H. Oliver, E. B. Thorstensen, A. L. Jaquiery, S. M. Husted, J. E. Harding, and F. H. Bloomfield
Effects of Twinning and Periconceptional Undernutrition on Late-Gestation Hypothalamic-Pituitary-Adrenal Axis Function in Ovine Pregnancy
Endocrinology,
March 1, 2008;
149(3):
1163 - 1172.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G. Bechtold, K. Vernon, T. Hines, and D. A. Scheuer
Genetic predisposition to hypertension sensitizes borderline hypertensive rats to the hypertensive effects of prenatal glucocorticoid exposure
J. Physiol.,
January 15, 2008;
586(2):
673 - 684.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Kajantie, K. Feldt, K. Raikkonen, D. I. W. Phillips, C. Osmond, K. Heinonen, A.-K. Pesonen, S. Andersson, D. J. P. Barker, and J. G. Eriksson
Body Size at Birth Predicts Hypothalamic-Pituitary-Adrenal Axis Response to Psychosocial Stress at Age 60 to 70 Years
J. Clin. Endocrinol. Metab.,
November 1, 2007;
92(11):
4094 - 4100.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chan, E. H Rabbitt, B. A Innes, J. N Bulmer, P. M Stewart, M. D Kilby, and M. Hewison
Glucocorticoid-induced apoptosis in human decidua: a novel role for 11{beta}-hydroxysteroid dehydrogenase in late gestation
J. Endocrinol.,
October 1, 2007;
195(1):
7 - 15.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Igosheva, P. D. Taylor, L. Poston, and V. Glover
Prenatal stress in the rat results in increased blood pressure responsiveness to stress and enhanced arterial reactivity to neuropeptide Y in adulthood
J. Physiol.,
July 15, 2007;
582(2):
665 - 674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Mairesse, J. Lesage, C. Breton, B. Breant, T. Hahn, M. Darnaudery, S. L. Dickson, J. Seckl, B. Blondeau, D. Vieau, et al.
Maternal stress alters endocrine function of the feto-placental unit in rats
Am J Physiol Endocrinol Metab,
June 1, 2007;
292(6):
E1526 - E1533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Bogdarina, S. Welham, P. J. King, S. P. Burns, and A. J.L. Clark
Epigenetic Modification of the Renin-Angiotensin System in the Fetal Programming of Hypertension
Circ. Res.,
March 2, 2007;
100(4):
520 - 526.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Goldman, G. Wood, M. B. Goldman, M. Gavin, S. Paul, S. Zaheer, G. Fayyaz, and R. S. Pilla
Diminished Glucocorticoid Negative Feedback in Polydipsic Hyponatremic Schizophrenic Patients
J. Clin. Endocrinol. Metab.,
February 1, 2007;
92(2):
698 - 704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hirvikoski, A. Nordenstrom, T. Lindholm, F. Lindblad, E. M. Ritzen, A. Wedell, and S. Lajic
Cognitive Functions in Children at Risk for Congenital Adrenal Hyperplasia Treated Prenatally with Dexamethasone
J. Clin. Endocrinol. Metab.,
February 1, 2007;
92(2):
542 - 548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Donn, A. Berry, A. Stevens, S. Farrow, J. Betts, R. Stevens, C. Clayton, J. Wang, L. Warnock, J. Worthington, et al.
Use of gene expression profiling to identify a novel glucocorticoid sensitivity determining gene, BMPRII
FASEB J,
February 1, 2007;
21(2):
402 - 414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Kajantie, D. I. W. Phillips, C. Osmond, D. J. P. Barker, T. Forsen, and J. G. Eriksson
Spontaneous Hypothyroidism in Adult Women Is Predicted by Small Body Size at Birth and during Childhood
J. Clin. Endocrinol. Metab.,
December 1, 2006;
91(12):
4953 - 4956.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Hewitt, P. J. Mark, and B. J. Waddell
Glucocorticoids Prevent the Normal Increase in Placental Vascular Endothelial Growth Factor Expression and Placental Vascularity during Late Pregnancy in the Rat
Endocrinology,
December 1, 2006;
147(12):
5568 - 5574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. KAJANTIE
Fetal Origins of Stress-Related Adult Disease
Ann. N.Y. Acad. Sci.,
November 1, 2006;
1083(1):
11 - 27.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Diego, N. A. Jones, T. Field, M. Hernandez-Reif, S. Schanberg, C. Kuhn, and A. Gonzalez-Garcia
Maternal psychological distress, prenatal cortisol, and fetal weight.
Psychosom Med,
September 1, 2006;
68(5):
747 - 753.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. YEHUDA
Advances in Understanding Neuroendocrine Alterations in PTSD and Their Therapeutic Implications
Ann. N.Y. Acad. Sci.,
July 1, 2006;
1071(1):
137 - 166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. SECKL and M. J. MEANEY
Glucocorticoid "Programming" and PTSD Risk
Ann. N.Y. Acad. Sci.,
July 1, 2006;
1071(1):
351 - 378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Hewitt, P. J. Mark, A. M. Dharmarajan, and B. J. Waddell
Placental Expression of Secreted Frizzled Related Protein-4 in the Rat and the Impact of Glucocorticoid-Induced Fetal and Placental Growth Restriction
Biol Reprod,
July 1, 2006;
75(1):
75 - 81.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. McArthur, Z.-L. Siddique, H. C. Christian, G. Capone, E. Theogaraj, C. D. John, S. F. Smith, J. F. Morris, J. C. Buckingham, and G. E. Gillies
Perinatal Glucocorticoid Treatment Disrupts the Hypothalamo-Lactotroph Axis in Adult Female, But Not Male, Rats
Endocrinology,
April 1, 2006;
147(4):
1904 - 1915.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Fowden, J. W. Ward, F. P. B. Wooding, A. J. Forhead, and M. Constancia
Programming placental nutrient transport capacity
J. Physiol.,
April 1, 2006;
572(1):
5 - 15.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Zandi-Nejad, V. A. Luyckx, and B. M. Brenner
Adult Hypertension and Kidney Disease: The Role of Fetal Programming
Hypertension,
March 1, 2006;
47(3):
502 - 508.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-H. Yao, L. Chen, and B. L. G. Nyomba
Adult rats prenatally exposed to ethanol have increased gluconeogenesis and impaired insulin response of hepatic gluconeogenic genes
J Appl Physiol,
February 1, 2006;
100(2):
642 - 648.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. T. Alexander
Fetal programming of hypertension
Am J Physiol Regulatory Integrative Comp Physiol,
January 1, 2006;
290(1):
R1 - R10.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Hewitt, P. J. Mark, and B. J. Waddell
Placental Expression of Peroxisome Proliferator-Activated Receptors in Rat Pregnancy and the Effect of Increased Glucocorticoid Exposure
Biol Reprod,
January 1, 2006;
74(1):
23 - 28.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. OLOVNIKOV
Lunasensor, Infradian Rhythms, Telomeres, and the Chronomere Program of Aging
Ann. N.Y. Acad. Sci.,
December 1, 2005;
1057(1):
112 - 132.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Russcher, P. Smit, E. L. T. van den Akker, E. F. C. van Rossum, A. O. Brinkmann, F. H. de Jong, S. W. J. Lamberts, and J. W. Koper
Two Polymorphisms in the Glucocorticoid Receptor Gene Directly Affect Glucocorticoid-Regulated Gene Expression
J. Clin. Endocrinol. Metab.,
October 1, 2005;
90(10):
5804 - 5810.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A M Welberg, K V Thrivikraman, and P. M Plotsky
Chronic maternal stress inhibits the capacity to up-regulate placental 11{beta}-hydroxysteroid dehydrogenase type 2 activity
J. Endocrinol.,
September 1, 2005;
186(3):
R7 - R12.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J.P. Barker and S. P. Bagby
Developmental Antecedents of Cardiovascular Disease: A Historical Perspective
J. Am. Soc. Nephrol.,
September 1, 2005;
16(9):
2537 - 2544.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. E. Hoy, M. D. Hughson, J. F. Bertram, R. Douglas-Denton, and K. Amann
Nephron Number, Hypertension, Renal Disease, and Renal Failure
J. Am. Soc. Nephrol.,
September 1, 2005;
16(9):
2557 - 2564.
[Full Text]
[PDF]
|
|
|
|
