Journal of Clinical Endocrinology & Metabolism, Vol 81, 3951-3960, Copyright © 1996 by Endocrine Society

ARTICLES

Cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate in the cerebrospinal fluid of man: relation to blood levels and the effects of age

EP Guazzo, PJ Kirkpatrick, IM Goodyer, HM Shiers and J Herbert
Department of Neurosurgery, University of Cambridge, United Kingdom.

The relation between blood and cerebrospinal fluid (CSF) concentrations of cortisol, dehydroepiandrosterone (DHEA), and its sulfate (DHEAS) was measured in 62 subjects aged 3-85 yr old, fitted with ventriculo- peritoneal or lumbar-peritoneal shunts for a variety of diagnoses. There were 36 males and 36 females. Forty-eight subjects were not taking exogenous corticosteroids; the other 14 were receiving either systemic or local steroids. A single sample of blood and CSF was taken from each subject within 10 min for measurement of cortisol, DHEA, and DHEAS. The proportional levels of cortisol (5.8%) and DHEA (5.4%) in the CSF compared with those in the blood were similar in subjects not taking steroids. However, CSF DHEAS levels were only 0.15% of those in the blood. Because DHEAS blood levels were so much greater than DHEA, DHEAS in the CSF was still higher than DHEA despite the reduced penetration of the sulfated steroid. The blood/CSF ratios were similar in subjects taking steroids. There were significant correlations in steroid-free subjects between blood and CSF levels for DHEA (r = 0.65) and DHEAS (r = 0.88) but not for cortisol (r = 0.26). Steroid treatment significantly lowered blood cortisol, DHEA and DHEAS, and CSF DHEA, but not CSF cortisol or DHEAS compared with an age- and sex-matched sample of steroid-free subjects. In steroid-free adults (18 yr and over; n = 37), blood cortisol showed no age-related change. However, CSF cortisol was markedly raised in a proportion of steroid-free subjects over the age of 60 yr. Levels of corticoid-binding globulin in plasma did not alter with age. As expected, there were significant age-related decrements in both blood DHEA and DHEAS. CSF DHEA (r = 0.42) and CSF DHEAS (r = 0.39) were significantly negatively correlated with age. In steroid-free juveniles (n = 11) there were no age-related changes in either blood or CSF cortisol, but significant increases with age in DHEA and DHEAS in both blood and CSF. Calculation of the cortisol/DHEA and cortisol/ DHEAS molar ratios in the CSF showed both to be raised in the very young (3-8 yr) and the elderly (60 yr and over) by a factor of 4-5 compared with young adults aged 18-39. There were no sex differences in any of the parameters measured. These findings show that the relation between levels in the blood and CSF differ for each of these three neuroactive steroids. The brain is exposed to relatively high levels of DHEA and DHEAS during later childhood and early adulthood but to relatively or absolutely high levels of cortisol during infancy and older age. In view of the known antiglucocorticoid action of DHEA and DHEAS, and the direct action of these steroids on membrane-bound transmitter events (such as gamma-aminobutyric acidA receptors), these changes may have important implications for age- related alterations in brain function.

This article has been cited by other articles:

				I. M. Goodyer, A. Bacon, M. Ban, T. Croudace, and J. Herbert Serotonin transporter genotype, morning cortisol and subsequent depression in adolescents The British Journal of Psychiatry, July 1, 2009; 195(1): 39 - 45. [Abstract] [Full Text] [PDF]

				M. Neu, M. L. Laudenslager, and J. Robinson Coregulation in Salivary Cortisol During Maternal Holding of Premature Infants Biol Res Nurs, January 1, 2009; 10(3): 226 - 240. [Abstract] [PDF]

				D. Knopman and V. W. Henderson DHEA for Alzheimer's disease: A modest showing by a superhormone Neurology, April 8, 2003; 60(7): 1060 - 1061. [Full Text] [PDF]

				R. D. Strous, R. Maayan, R. Lapidus, R. Stryjer, M. Lustig, M. Kotler, and A. Weizman Dehydroepiandrosterone Augmentation in the Management of Negative, Depressive, and Anxiety Symptoms in Schizophrenia Arch Gen Psychiatry, February 1, 2003; 60(2): 133 - 141. [Abstract] [Full Text] [PDF]

				Z A Erkut, E Endert, I Huitinga, and D F Swaab Cortisol is increased in postmortem cerebrospinal fluid of multiple sclerosis patients: relationship with cytokines and sepsis Multiple Sclerosis, June 1, 2002; 8(3): 229 - 236. [Abstract] [PDF]

				C. R. Pryce, R. Palme, and J. Feldon Development of Pituitary-Adrenal Endocrine Function in the Marmoset Monkey: Infant Hypercortisolism Is the Norm J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 691 - 699. [Abstract] [Full Text] [PDF]

				I. M. GOODYER, R. J. PARK, C. M. NETHERTON, and J. HERBERT Possible role of cortisol and dehydroepiandrosterone in human development and psychopathology The British Journal of Psychiatry, September 1, 2001; 179(3): 243 - 249. [Abstract] [Full Text] [PDF]

				L. Ibáñez, J. DiMartino-Nardi, N. Potau, and P. Saenger Premature Adrenarche--Normal Variant or Forerunner of Adult Disease? Endocr. Rev., December 1, 2000; 21(6): 671 - 696. [Abstract] [Full Text]

				P. J. Hunt, E. M. Gurnell, F. A. Huppert, C. Richards, A. T. Prevost, J. A. H. Wass, J. Herbert, and V. K. K. Chatterjee Improvement in Mood and Fatigue after Dehydroepiandrosterone Replacement in Addison's Disease in a Randomized, Double Blind Trial J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4650 - 4656. [Abstract] [Full Text]

				T.O. HARRIS, S. BORSANYI, S. MESSARI, K. STANFORD, G.W. BROWN, S.E. CLEARY, H.M. SHIERS, and J. HERBERT Morning cortisol as a risk factor for subsequent major depressive disorder in adult women The British Journal of Psychiatry, December 1, 2000; 177(6): 505 - 510. [Abstract] [Full Text] [PDF]

				S. D. Moffat, A. B. Zonderman, S. M. Harman, M. R. Blackman, C. Kawas, and S. M. Resnick The Relationship Between Longitudinal Declines in Dehydroepiandrosterone Sulfate Concentrations and Cognitive Performance in Older Men Arch Intern Med, July 24, 2000; 160(14): 2193 - 2198. [Abstract] [Full Text] [PDF]

				M. Bergendahl, A. Iranmanesh, T. Mulligan, and J. D. Veldhuis Impact of Age on Cortisol Secretory Dynamics Basally and as Driven by Nutrient-Withdrawal Stress J. Clin. Endocrinol. Metab., June 1, 2000; 85(6): 2203 - 2214. [Abstract] [Full Text]

				I. M. GOODYER, J. HERBERT, A. TAMPLIN, and P. M. E. ALTHAM First-episode major depression in adolescents: Affective, cognitive and endocrine characteristics of risk status and predictors of onset The British Journal of Psychiatry, February 1, 2000; 176(2): 142 - 149. [Abstract] [Full Text] [PDF]

				I. H. Zwain and S. S. C. Yen Dehydroepiandrosterone: Biosynthesis and Metabolism in the Brain Endocrinology, February 1, 1999; 140(2): 880 - 887. [Abstract] [Full Text]

				S. Kalmijn, L. J. Launer, R. P. Stolk, F. H. de Jong, H. A. P. Pols, A. Hofman, M. M. B. Breteler, and S. W. J. Lamberts A Prospective Study on Cortisol, Dehydroepiandrosterone Sulfate, and Cognitive Function in the Elderly J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3487 - 3492. [Abstract] [Full Text]

				M. Boscaro, A. Paoletta, E. Scarpa, L. Barzon, P. Fusaro, F. Fallo, and N. Sonino Age-Related Changes in Glucocorticoid Fast Feedback Inhibition of Adrenocorticotropin in Man J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1380 - 1383. [Abstract] [Full Text]

				V. G. Kimonides, N. H. Khatibi, C. N. Svendsen, M. V. Sofroniew, and J. Herbert Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity PNAS, February 17, 1998; 95(4): 1852 - 1857. [Abstract] [Full Text] [PDF]