| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Divisions of Medical Pharmacology (A.M.K., O.C.M., E.R.d.K.) and Pharmacology (I.C.J.v.d.S., E.C.M.d.L., A.G.d.B.), Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, 2300 RA, The Netherlands; and Institute for Neurobiology (P.J.L.), University of Amsterdam, 1090 GB, Amsterdam, The Netherlands
Address all correspondence and requests for reprints to: A. M. Karssen, Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, P.O. Box 9503, Leiden University, Leiden, 2300 RA, The Netherlands. E-mail: Karssen{at}LACDR.LeidenUniv.nl
In the present study, we investigated the role of the multidrug resistance (mdr) P-glycoprotein (Pgp) at the blood-brain barrier in the control of access of cortisol and corticosterone to the mouse and human brain.
[3H]Cortisol poorly penetrated the brain of adrenalectomized wild-type mice, but the uptake was 3.5-fold enhanced after disruption of Pgp expression in mdr 1a-/- mice. In sharp contrast, treatment with [3H]corticosterone revealed high labeling of brain tissue without difference between both genotypes.
Interestingly, human MDR1 Pgp also differentially transported cortisol and corticosterone. LLC-PK1 monolayers stably transfected with MDR1 complementary DNA showed polar transport of [3H]cortisol that could be blocked by a specific Pgp blocker, whereas [3H]corticosterone transport did not differ between transfected and host cells.
Determination of the concentration of both steroids in extracts of human postmortem brain tissue using liquid chromatography mass spectrometry revealed that the ratio of corticosterone over cortisol in the brain was significantly increased relative to plasma.
In conclusion, the data demonstrate that in both mouse and human brain the penetration of cortisol is less than that of corticosterone. This finding suggests a more prominent role for corticosterone in control of human brain function than hitherto recognized.
This article has been cited by other articles:
 |
|
 |
|
  B. L. Mason, C. M. Pariante, and S. A. Thomas A Revised Role for P-Glycoprotein in the Brain Distribution of Dexamethasone, Cortisol, and Corticosterone in Wild-Type and ABCB1A/B-Deficient Mice Endocrinology, October 1, 2008; 149(10): 5244 - 5253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. de Kloet and R. A. Sarabdjitsingh Everything Has Rhythm: Focus on Glucocorticoid Pulsatility Endocrinology, July 1, 2008; 149(7): 3241 - 3243. [Full Text] [PDF]
|
|
|
|
|
|
S. K. Droste, L. de Groote, H. C. Atkinson, S. L. Lightman, J. M. H. M. Reul, and A. C. E. Linthorst Corticosterone Levels in the Brain Show a Distinct Ultradian Rhythm but a Delayed Response to Forced Swim Stress Endocrinology, July 1, 2008; 149(7): 3244 - 3253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Schmidt and K. K. Soma Cortisol and corticosterone in the songbird immune and nervous systems: local vs. systemic levels during development Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R103 - R110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ye, C. J Kenyon, S. M MacKenzie, K. Nichol, J. R Seckl, R. Fraser, J. M C Connell, and E. Davies Effects of ACTH, dexamethasone, and adrenalectomy on 11{beta}-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat central nervous system J. Endocrinol., February 1, 2008; 196(2): 305 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sanderson, A. Khan, and S. Thomas Distribution of Suramin, an Antitrypanosomal Drug, across the Blood-Brain and Blood-Cerebrospinal Fluid Interfaces in Wild-Type and P-Glycoprotein Transporter-Deficient Mice Antimicrob. Agents Chemother., September 1, 2007; 51(9): 3136 - 3146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. McEwen Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain Physiol Rev, July 1, 2007; 87(3): 873 - 904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Mark and B. J. Waddell P-Glycoprotein Restricts Access of Cortisol and Dexamethasone to the Glucocorticoid Receptor in Placental BeWo Cells Endocrinology, November 1, 2006; 147(11): 5147 - 5152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Arya, V. G. Demarco, M. Issar, and G. Hochhaus CONTRARY TO ADULT, NEONATAL RATS SHOW PRONOUNCED BRAIN UPTAKE OF CORTICOSTEROIDS Drug Metab. Dispos., June 1, 2006; 34(6): 939 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Samtani, N. A. Pyszczynski, D. C. DuBois, R. R. Almon, and W. J. Jusko Modeling Glucocorticoid-Mediated Fetal Lung Maturation: I. Temporal Patterns of Corticosteroids in Rat Pregnancy J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 117 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Goralski, P. D. Acott, A. D. Fraser, D. Worth, and C. J. Sinal BRAIN CYCLOSPORIN A LEVELS ARE DETERMINED BY ONTOGENIC REGULATION OF MDR1A EXPRESSION Drug Metab. Dispos., February 1, 2006; 34(2): 288 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Karssen, O. C. Meijer, A. Berry, R. Sanjuan Pinol, and E. R. de Kloet Low Doses of Dexamethasone Can Produce a Hypocorticosteroid State in the Brain Endocrinology, December 1, 2005; 146(12): 5587 - 5595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Kalabis, A. Kostaki, M. H. Andrews, S. Petropoulos, W. Gibb, and S. G. Matthews Multidrug Resistance Phosphoglycoprotein (ABCB1) in the Mouse Placenta: Fetal Protection Biol Reprod, October 1, 2005; 73(4): 591 - 597. [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]
|
|
|
|
 |
|
 G. A. Lodygensky, K. Rademaker, S. Zimine, M. Gex-Fabry, A. F. Lieftink, F. Lazeyras, F. Groenendaal, L. S. de Vries, and P. S. Huppi Structural and Functional Brain Development After Hydrocortisone Treatment for Neonatal Chronic Lung Disease Pediatrics, July 1, 2005; 116(1): 1 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Baker, N. N. Ekhator, J. W. Kasckow, B. Dashevsky, P. S. Horn, L. Bednarik, and T. D. Geracioti Jr. Higher Levels of Basal Serial CSF Cortisol in Combat Veterans With Posttraumatic Stress Disorder Am J Psychiatry, May 1, 2005; 162(5): 992 - 994. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Grauer and M. Uhr P-glycoprotein reduces the ability of amitriptyline metabolites to cross the blood brain barrier in mice after a 10-day administration of amitriptyline J Psychopharmacol, March 1, 2004; 18(1): 66 - 74. [Abstract] [PDF]
|
|
|
|
|
|
C. L. Raison and A. H. Miller When Not Enough Is Too Much: The Role of Insufficient Glucocorticoid Signaling in the Pathophysiology of Stress-Related Disorders Am J Psychiatry, September 1, 2003; 160(9): 1554 - 1565. [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 |
