Age-Related Changes in Hypothalamic-Pituitary-Adrenal Axis Activity of Male C57BL/6J MiceDalm S.a · Enthoven L.a · Meijer O.C.a · van der Mark M.H.a · Karssen A.M.a, b · de Kloet E.R.a · Oitzl M.S.a
aDivision of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden University, Leiden, The Netherlands; bStanford University School of Medicine, Department of Psychiatry and Behavioral Sciences MSLS, Palo Alto, Calif., USA
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
As there is little known about age-related changes in the hypothalamic-pituitary-adrenal (HPA) axis of mice, we determined the daily patterns of corticosterone secretion every 2 h, together with adrenocorticotropic hormone (ACTH) release and central HPA axis markers in the morning and evening of 3-, 9- and 16-month-old male C57BL/6J mice. We observed that: (i) corticosterone secretion showed a distinct age-related circadian pattern. During the light period this was expressed by relative hypercorticism in 9-month-old mice and relative hypocorticism in 16-month-old mice. ACTH was elevated at 16 months of age; (ii) mineralocorticoid (MR) and glucocorticoid receptor (GR) mRNA expression in the hippocampus was significantly decreased in 9-month-old mice, whereas in 16-month-old mice, expression was similar to young animals. Circadian variation was modest in all age groups; (iii) the parvocellular hypothalamic paraventricular nucleus (PVN) expressed very high vasopressin mRNA, which was subject to circadian variation in 3- and 9-month-old mice. Furthermore, significant levels of MR mRNA were expressed in the PVN. In conclusion, basal HPA axis activity and expression of its central regulatory markers are age-dependent in mice. This suggests that the capacity to adjust to environmental demands is either a function of age, or depends on different dynamics of the HPA axis.
© 2005 S. Karger AG, Basel
Dallman MF: Glucocorticoid negative feedback; in Fink G (ed): Encyclopedia of Stress. New York, Academic Press, 2000, vol 2, pp 224–228.
- Reul JM, de Kloet ER: Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology 1985;117:2505–2511.
- Windle RJ, Wood SA, Shanks N, Lightman SL, Ingram CD: Ultradian rhythm of basal corticosterone release in the female rat: dynamic interaction with the response to acute stress. Endocrinology 1998;139:443–450.
- De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M: Brain corticosteroid receptor balance in health and disease. Endocr Rev 1998;19:269–301.
- Akana SF, Cascio CS, Du JZ, Levin N, Dallman MF: Reset of feedback in the adrenocortical system: an apparent shift in sensitivity of adrenocorticotropin to inhibition by corticosterone between morning and evening. Endocrinology 1986;119:2325–2332.
Buijs RM, Kalsbeek A, van der Woude TP, van Heerikhuize JJ, Shinn S: Suprachiasmatic nucleus lesion increases corticosterone secretion. Am J Physiol 1993;264:R1186–R1192.
- Spencer RL, Miller AH, Moday H, Stein M, McEwen BS: Diurnal differences in basal and acute stress levels of type I and type II adrenal steroid receptor activation in neural and immune tissues. Endocrinology 1993;133:1941–1950.
- Peeters F, Nicolson NA, Berkhof J: Levels and variability of daily life cortisol secretion in major depression. Psychiatry Res 2004;126:1–13.
- Hatfield CF, Herbert J, van Someren EJ, Hodges JR, Hastings MH: Disrupted daily activity/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer’s dementia. Brain 2004;127:1061–1074.
- Lupien SJ, Wan N: Successful ageing: from cell to self. Philos Trans R Soc Lond B Biol Sci 2004;359:1413–1426.
- Sapolsky RM: Glucocorticoids, stress, and their adverse neurological effects: relevance to aging. Exp Gerontol 1999;34:721–732.
- Herman JP, Larson BR, Speert DB, Seasholtz AF: Hypothalamo-pituitary-adrenocortical dysregulation in aging F344/Brown-Norway F1 hybrid rats. Neurobiol Aging 2001;22:323–332.
Van Eekelen JA, Oitzl MS, de Kloet ER: Adrenocortical hyporesponsiveness and glucocorticoid feedback resistance in old male Brown Norway rats. J Gerontol A Biol Sci Med Sci 1995;50:B83–B89.
- Bizon JL, Helm KA, Han JS, Chun HJ, Pucilowska J, Lund PK,et al: Hypothalamic-pituitary-adrenal axis function and corticosterone receptor expression in behaviourally characterized young and aged Long-Evans rats. Eur J Neurosci 2001;14:1739–1751.
Cai A, Wise PM: Age-related changes in the diurnal rhythm of CRH gene expression in the paraventricular nuclei. Am J Physiol 1996;270:E238–E243.
- Bazhanova ED, Chernigovskaya EV, Danilova OA: Different pathways of neurohormonal hypothalamic control of the adrenal cortex function in young and old rats. Mech Ageing Dev 2000;118:91–102.
- Workel JO, Oitzl MS, Fluttert M, Lesscher H, Karssen A, de Kloet ER: Differential and age-dependent effects of maternal deprivation on the hypothalamic-pituitary-adrenal axis of Brown Norway rats from youth to senescence. J Neuroendocrinol 2001;13:569–580.
- Grootendorst J, Enthoven L, Dalm S, de Kloet ER, Oitzl MS: Increased corticosterone secretion and early-onset of cognitive decline in female apolipoprotein E-knockout mice. Behav Brain Res 2004;148:167–177.
- Talan MI, Ingram DK: Age comparisons of body temperature and cold tolerance among different strains of Mus musculus. Mech Ageing Dev 1986;33:247–256.
- Durschlag M, Wurbel H, Stauffacher M, Von Holst D: Repeated blood collection in the laboratory mouse by tail incision – modification of an old technique. Physiol Behav 1996;60:1565–1568.
- Schmidt M, Enthoven L, van der MM, Levine S, de Kloet ER, Oitzl MS: The postnatal development of the hypothalamic-pituitary-adrenal axis in the mouse. Int J Dev Neurosci 2003;21:125–132.
- Meaney MJ, Aitken DH, Sharma S, Viau V: Basal ACTH, corticosterone and corticosterone-binding globulin levels over the diurnal cycle, and age-related changes in hippocampal type I and type II corticosteroid receptor binding capacity in young and aged, handled and nonhandled rats. Neuroendocrinology 1992;55:204–213.
- Watts AG, Tanimura S, Sanchez-Watts G: Corticotropin-releasing hormone and arginine vasopressin gene transcription in the hypothalamic paraventricular nucleus of unstressed rats: daily rhythms and their interactions with corticosterone. Endocrinology 2004;145:529–540.
- Atkinson HC, Waddell BJ: Circadian variation in basal plasma corticosterone and adrenocorticotropin in the rat: sexual dimorphism and changes across the estrous cycle. Endocrinology 1997;138:3842–3848.
- Bradbury MJ, Akana SF, Dallman MF: Roles of type I and II corticosteroid receptors in regulation of basal activity in the hypothalamo-pituitary-adrenal axis during the diurnal trough and the peak: Evidence for a nonadditive effect of combined receptor occupation. Endocrinology 1994;134:1286–1296.
- Magri F, Locatelli M, Balza G, Molla G, Cuzzoni G, Fioravanti M,et al: Changes in endocrine circadian rhythms as markers of physiological and pathological brain aging. Chronobiol Int 1997;14:385–396.
- Carnes M, Goodman BM, Lent SJ, Vo H, Jaeckels R: Coincident plasma ACTH and corticosterone time series: Comparisons between young and old rats. Exp Gerontol 1994;29:625–643.
- Van Eekelen JA, Rots NY, Sutanto W, Oitzl MS, de Kloet ER: Brain corticosteroid receptor gene expression and neuroendocrine dynamics during aging. J Steroid Biochem Mol Biol 1991;40:679–683.
- Holmes MC, French KL, Seckl JR: Dysregulation of diurnal rhythms of serotonin 5-HT2C and corticosteroid receptor gene expression in the hippocampus with food restriction and glucocorticoids. J Neurosci 1997;17:4056–4065.
- Cizza G, Gold PW, Chrousos GP: Aging is associated in the 344/N Fischer rat with decreased stress responsivity of central and peripheral catecholaminergic systems and impairment of the hypothalamic-pituitary-adrenal axis. Ann NY Acad Sci 1995;771:491–511.
- Kalsbeek A, Palm IF, Buijs RM: Central vasopressin systems and steroid hormones. Prog Brain Res 2002;139:57–73.
- Keck ME, Hatzinger M, Wotjak CT, Landgraf R, Holsboer F, Neumann ID: Ageing alters intrahypothalamic release patterns of vasopressin and oxytocin in rats. Eur J Neurosci 2000;12:1487–1494.
- Zhou JN, Swaab DF: Activation and degeneration during aging: a morphometric study of the human hypothalamus. Microsc Res Tech 1999;44:36–48.
- Itoi K, Jiang YQ, Iwasaki Y, Watson SJ: Regulatory mechanisms of corticotropin-releasing hormone and vasopressin gene expression in the hypothalamus. J Neuroendocrinol 2004;16:348–355.
- Grillo CA, Saravia F, Ferrini M, Piroli G, Roig P, Garcia SI,et al: Increased expression of magnocellular vasopressin mRNA in rats with deoxycorticosterone-acetate induced salt appetite. Neuroendocrinology 1998;68:105–115.
- Herman JP, Spencer R: Regulation of hippocampal glucocorticoid receptor gene transcription and protein expression in vivo. J Neurosci 1998;18:7462–7473.
- Spencer RL, Kim PJ, Kalman BA, Cole MA: Evidence for mineralocorticoid receptor facilitation of glucocorticoid receptor-dependent regulation of hypothalamic-pituitary-adrenal axis activity. Endocrinology 1998;139:2718–2726.
- Kovacs KJ, Foldes A, Sawchenko PE: Glucocorticoid negative feedback selectively targets vasopressin transcription in parvocellular neurosecretory neurons. J Neurosci 2000;20:3843–3852.
- Sawchenko PE: Evidence for differential regulation of corticotropin-releasing factor and vasopressin immunoreactivities in parvocellular neurosecretory and autonomic-related projections of the paraventricular nucleus. Brain Res 1987;437:253–263.
- Ratka A, Sutanto W, Bloemers M, de Kloet ER: On the role of brain mineralocorticoid (type I) and glucocorticoid (type II) receptors in neuroendocrine regulation. Neuroendocrinology 1989;50:117–123.
- De Kloet ER, Sutanto W, van den Berg DT, Carey MP, van Haarst AD, Hornsby CD,et al: Brain mineralocorticoid receptor diversity: functional implications. J Steroid Biochem Mol Biol 1993;47:183–190.
- Murphy EK, Spencer RL, Sipe KJ, Herman JP: Decrements in nuclear glucocorticoid receptor protein levels and DNA binding in aged rat hippocampus. Endocrinology 2002;143:1362–1370.
- Ma XM, Aguilera G: Differential regulation of corticotropin-releasing hormone and vasopressin transcription by glucocorticoids. Endocrinology 1999;140:5642–5650.
- De Kloet ER, Oitzl MS, Joels M: Stress and cognition: Are corticosteroids good or bad guys? Trends Neurosci 1999;22:422–426.
- Oitzl MS, Workel JO, Fluttert M, Frosch F, de Kloet ER: Maternal deprivation affects behaviour from youth to senescence: amplification of individual differences in spatial learning and memory in senescent Brown Norway rats. Eur J Neurosci 2000;12:3771–3780.
Everitt A, Meites J: Aging and anti-aging effects of hormones. J Gerontol 1989;44:B139–B147.
- Meijer OC, Topic B, Steenbergen PJ, Jocham G, Huston JP, Oitzl MS: Correlations between hypothalamus-pituitary-adrenal axis parameters depend on age and learning capacity. Endocrinology 2005;146:1372–1381.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.