Advertisement
Comment| Volume 27, ISSUE 9, P937-952, May 01, 1990

Download started.

Ok

Hypercortisolism and its possible neural bases

DOI:https://doi.org/10.1016/0006-3223(90)90032-W
Hypercortisolism and its possible neural bases
Next ArticleInteractions of corticotropin-releasing factor with antidepressant and anxiolytic drugs: Behavioral studies with pigeons
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      As is clear from the pages of this journal, biological psychiatrists remain fascinated by the phenomenon of dexamethasone (DEX) resistance and the hypercorticosolism of various neuropsychiatric disorders. The mere existence of the endocrine abnormalities attests to the biological reality of these disorders. Furthermore, progress continues in using the occurence of these endocrine defects as both diagnostic and prognostic markers of disease subtypes.
      Progress has also been made in understanding the mechanisms underlying the endocrine defects. The adrenocortical axis is vastly complex, involving multiple hypothalamic-releasing factors under CNS control, shifting pituitary and adrenal sensitivies to hormonal signals, and feedback regulation at all three levels. What defects within this system produce DEX resistance and hypercortisolism? In this paper, we review data suggesting that the endocrine problems is, at least in part, neural in nature. Drawing upon a rodent literature, we will also suggest some models by which this can occur. The hypercorticolism found in cases of affective disorders, anorexia nervosa, Alzheimer's disease, among the very aged or the chronically stressed, is not a uniform phenomenon. Basal cortisol concentrations can be elevated in all or part of the circadian cycle. Resistance to glucocorticoid (GC) feedback inhibition (as typically demonstrated by DEX resistance) can occur; the resistance can be complete, or occur as early escape from DEX suppression. Finally, elevated basal cortisol concentrations and DEX resistance can occur independently of each other. Until the end of this review, we will conveniently refer to these variants of adrenocortical hyperactivity as “hypercortisolism”. In addition, rather than using the term “hypercortisolism” for the rat, we will use “hyperadrenocorticism” (as they secrete corticosterone, rather than cortisol).
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Akana S.
        • Dallman M.
        Low levels of corticosterone reverse adrenalectomy-induced immunohistochemical staining of CRF and vasopressin in the paraventricular nucleus of adrenalectomized rats.
        Soc Neurosci Abstr. 1987; 450: 6
        • Amsterdam J.
        • Marinelli D.
        • Arger P.
        • Winokur A.
        Assessment of adrenal gland volume by computed tomography in depressed patients and healthy volunteers: A pilot study.
        Psychiatr Res. 1987; 21: 189-197
        • Angelucci L.
        • Valeri P.
        • Grossi E.
        Involvement of hippocampal corticosterone receptors in behavioral phenomena.
        in: Brambilla G. Racagni G. de Wied D. Progress in Psychoneuroendocrinology. Elsevier, Amsterdam1980: 186-199
        • Anisman H.
        • Zacharko R.
        Depression: the predisposing influence of stress.
        Behav Brain Sci. 1982; 5: 89-106
        • Antoni F.
        Hypothalamic control of adrenocorticotropic hormone secretion: Advances since the discovery of 41-residue corticotropin-releasing factor.
        Endocr Rev. 1986; 7: 351-373
        • APA Taskforce on Laboratory Tests in Psychiatry
        The dexamethasone suppression test. An overview of its current status in psychiatry.
        Am J Psychiatry. 1987; 144: 1253-1268
        • Banki C.
        • Bissette G.
        • Arato M.
        • O'Conner L.
        • Nemeroff C.
        CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia.
        Am J Psychiatry. 1987; 144: 7-11
        • Bardeleben U.von
        • Holsber F.
        • Stalla G.
        • Muller O.
        Combined administration of human corticotropin-releasing factor and lysine vasopressin induced cortisol escape from dexamethasone suppression in healthy subjects.
        Life Sci. 1985; 37: 1613-1618
        • Baumgartner A.
        • Graf K.
        • Kurten I.
        The dexamethasone suppression test in depression, in schizaphrenia, and during experimental stress.
        Biol Psychiatry. 1985; 29: 675-681
        • Blichert-Toft B.
        • Blichert-Toft M.
        Adrenocortical function in the aged assessed by the rapid corticotropin test.
        Acta Endocrinol (Copenh). 1970; 64: 410-419
        • Carroll B.
        Stimulation tests in depression.
        in: Carroll B. Depressive Illness: Some Research Studies. Elsevier, New York1972: 151-153
        • Cartlidge N.
        • Black M.
        • Hall M.
        Pituitary function in the elderly.
        Gerontol Clinic. 1970; 12: 65-74
        • Ceulemans D.
        • Westenberg H.
        • van Praag H.
        The effects of stress on the dexamethasone suppression test.
        Psychiatr Res. 1985; 14: 189-196
        • Coleman P.
        • Flood D.
        Neuron numbers and dendritic extent in normal aging and Alzheimer's disease.
        Neurobiol Aging. 1987; 8: 521-540
        • Davis K.
        • Davis B.
        • Mathe A.
        Age and the dexamethasone suppression test.
        Am J Psychiatry. 1984; 141: 872-876
        • De Leon M.
        • McRae T.
        • Tsai J.
        • George A.
        • Marcus D.
        • Freedman M.
        • Wolf A.
        • McEwen B.
        Abnormal cortisol response in Alzheimer's disease linked to hippocampal atrophy.
        Lancet. 1988; 13 (August): 391-392
        • Dorovini-Zis K.
        • Zis A.
        Increased adrenal weight in victims of violent suicide.
        Am J Psychiatry. 1987; 144: 1214-1215
        • Dunn J.
        • Orr S.
        Differential plasma corticosterone responses to hippocampal stimulation.
        Exp Brain Res. 1984; 54: 1-9
        • Dupont A.
        • Bastarache E.
        • Endroczi E.
        Hippocampal stimulation on plasma thyrotropin and corticosterone responses to acute cold-exposure in rat.
        Can J Physiol Pharmacol. 1972; 50: 364-369
        • Endroczi E.
        • Lissak K.
        • Bohus B.
        The inhibitory influence of archicortical structures on pituitary adrenal function.
        Acta Physiol Acad Sci Hung. 1959; 16: 17-21
        • Feldman S.
        • Chowers I.
        • Conforti N.
        Effect of dexamethasone on adrenocortical response in intact and hypothalamic deafferented rats.
        Acta Endocrinol (Copenh). 1973; 73: 660-666
        • Feldman S.
        • Conforti N.
        Feedback effects of dexamethasone on adrenocortical responses of rats with fornix section.
        Horm Res. 1976; 7: 56-60
        • Feldman S.
        • Conforti N.
        Participation of the dorsal hippocampus in the glucocorticoid feedback effect on adrenocortical activity.
        Neuroendocrinology. 1980; 30: 52-56
        • Fendler K.
        • Karmos G.
        • Telegdy M.
        The effect of hippocampal lesions on pituitary-adrenal function.
        Acta Endocrinol (Copenh). 1961; 73: 660-665
        • Ferrier I.
        • Pascual J.
        • Charlton B.
        • Wright C.
        • Leake A.
        Cortisol, ACTH and dexamethasone concentrations in a psychogeriatric population.
        Biol Psychiatry. 1988; 23: 252-261
        • Fischette C.
        • Komisurak B.
        • Ediner H.
        Differential fornix ablations and the circadian rhythmicity of adrenal corticosterone secretion.
        Brain Res. 1980; 195: 373-382
        • Fogel B.
        • Satel S.
        • Levy S.
        Occurrence of high concentrations of postdexamethasone cortisol in elderly psychiatric inpatients.
        Psychiatry Res. 1985; 15: 85-92
        • Garrick N.
        • Hill J.
        • Szele F.
        • Tomai T.
        • Gold P.
        • Murphy D.
        Corticotropin-releasing factor: a marked circadian rhythm in primate cerebrospinal fluid peaks in the evening and is inversely related to the cortisol circadian rhythm.
        Endocrinology. 1987; 121: 1329-1338
        • Gerkin A.
        • Holsboer F.
        Cortisol and corticosterone response after syn-corticotropin in relationship to suppressibility of cortisol.
        Psychoneuroendocrinology. 1986; 11: 185-192
        • Gerlach J.
        • McEwen B.
        • Pfaff D.
        Cells in regions of rhesus monkey brain and pituitary retain radioactive estradiol, corticosterone and cortisol differentially.
        Brain Res. 1976; 103: 603-615
        • Gold P.
        • Loriaux L.
        • Roy A.
        Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing's disease.
        N Engl J Med. 1986; 314: 1329-1335
        • Greden J.
        • Flegel P.
        • Haskett R.
        • Dilsaver S.
        • Carroll B.
        • Grunhaus L.
        Age effects in serial hypothalamic-pituitary-adrenal monitoring.
        Psychoneuroendocrinology. 1986; 11: 195-203
        • Greenwald B.
        • Mathe A.
        • Mohs R.
        • Levy M.
        • Johns C.
        • Davis K.
        Cortisol in Alzheimer's disease. II. Dexamethasone suppression, dementia severity and affective symptoms.
        Am J Psychiatry. 1986; 143: 442-449
        • Halbreich U.
        • Asnis G.
        • Zumoff B.
        • Nathan R.
        • Shindledecker R.
        Effect of age and sex on cortisol secretion in depressives and normals.
        Psychiatry Res. 1984; 13: 221-226
        • Herevanian B.
        • Woolf P.
        • Iker H.
        Plasma ACTH levels in depression before and after recovery: Relationship to the dexamethasone suppression test.
        Psychiatry Res. 1983; 10: 175-183
        • Hermus A.
        • Pieters G.
        • Pesman G.
        • Hofman J.
        • Smals G.
        • Benraad T.
        • Kloppenborg P.
        Escape from dexamethasone-induced ACTH and cortisol suppression by corticotropin-releasing hormone: Modulatory effect of basal dexamethasone levels.
        Clin Endocrinol. 1987; 26: 67-74
        • Holsboer F.
        • Bardeleben U.von
        • Gerken A.
        Blunted corticotropin and normal cortisol response to human corticotropin-releasing factor in depression.
        N Engl J Med. 1984; 311: 1127-1131
        • Holsboer F.
        • Bardeleben U.von
        • Wiedemann K.
        • Muller O.
        • Stalla G.
        Serial assessment of corticotropin-releasing hormone response after dexamethasone in depression: Implications for pathophysiology of DST nonsuppression.
        Biol Psychiatry. 1987; 22: 228-233
        • Jacobs S.
        • Mason J.
        • Kosten T.
        • Brown S.
        • Ostfeld A.
        Urinary-free cortisol excretion in relation to age in acutely stressed persons with depressive symptoms.
        Psychosom Med. 1984; 46: 213-217
        • Jensen H.
        • Blichert-Toft M.
        Serum corticotropin, plasma cortisol, and urinary excretion of 17-ketogenic steroids in the elderly (age group 66–94 years).
        Acta Endocrinol (Copenh). 1971; 66: 25-34
        • Kalin N.
        • Cohen R.
        • Kraemer G.
        The dexamethasone suppression test as a measure of hypothalamic-pituitary feedback sensitivity and its relationship to behavioral arousal.
        Neuroendocrinology. 1981; 32: 92-95
        • Kalin N.
        • Shelton S.
        • Barksdale C.
        • Brownfield M.
        A diurnal rhythm in cerebrospinal fluid corticotropin-releasing hormone different from the rhythm of pituitary-adrenal activity.
        Brain Res. 1987; 426: 385-390
        • Kant G.
        • Meyerhoff J.
        • Jarrad L.
        Biochemical indices of reactivity and habituation in rats with hippocampal lesions.
        Pharmacol Biochem Behav. 1984; 20: 793-797
        • Keller-Wood M.
        • Dallman M.
        Corticosteroid inhibition of ACTH secretion.
        Endocr Rev. 1984; 5: 1-24
        • Kley H.
        • Nieschlag E.
        • Kruskemper H.
        Age dependence of plasma oestrogen response to HCG and ACTH in men.
        Acta Endocrinol (Copenh). 1975; 79: 95-106
        • Kim C.
        • Kim C.
        Effect of partial hippocampal resection on stress mechanisms in rats.
        Am J Physiol. 1961; 201: 337-342
        • Knigge K.
        • Hays M.
        Evidence of inhibitive role of hippocampus in neural regulation of ACTH release.
        in: Proc Soc Exp Biol Med. 114. 1963: 67-70
        • Kovacs K.
        • Kiss J.
        • Makara G.
        Glucocorticoid implants around the hypothalamic paraventricular nucleus prevent the increase of corticotropin-releasing factor and arginine vasopressin immunostaining induced by adrenalectomy.
        Neuroendocrinology. 1986; 44: 229-234
        • Krahn D.
        • Meller W.
        • Shafter R.
        • Morley J.
        Cortisol response to vasopressin in depression.
        Biol Psychiatry. 1985; 20: 918-921
        • Lambert S.
        • Bons E.
        • Zuiderwijk J.
        High concentrations of catecholamines selectively diminish the sensitivity of CRF-stimulated ACTH release by cultured rat pituitary cells to the suppressive effects of dexamethasone.
        Life Sci. 1986; 39: 97-102
        • Levin N.
        • Shinsako J.
        • Dallman M.
        Corticosterone acts on the brain to inhibit adrenalectomy-induced adrenocorticotropin secretion.
        Endocrinology. 1988; 122: 694-700
        • Lewis D.
        • Pfohl B.
        • Schlechte J.
        • Coryell W.
        Influence of age on the cortisol response to dexamethasone.
        Psychiatr Res. 1984; 13: 213-219
        • Linkowsky P.
        • Mendlewicz J.
        • Kerkhofs M.
        • Leclercq R.
        • Golstein J.
        • Brasseur M.
        • Copinschi G.
        • Van Cauter E.
        24-Hour profile of adrenocorticotropin, cortisol and growth hormone in major depressive illness: effect of antidepressant treatment.
        J Clin Endocrinol Metab. 1987; 65: 141-148
        • Lowry M.
        • Meltzer H.
        Dex bioavailability: Implications for DST research.
        Biol Psychiatry. 1987; 22: 373-381
        • Mandell A.
        • Chapman L.
        • Rand R.
        Plasma corticosteroids: changes in concentrations after stimulation of hippocampus and amygdala.
        Science. 1963; 139: 1212-1215
        • Meaney M.
        • Aitken D.
        • Bhatnager S.
        • van Berkel C.
        • Sapolsky R.
        Effect of neonatal handling on age-related impairments associated with the hippocampus.
        Science. 1988; 239: 766-768
        • Moberg G.
        • Scapagnini U.
        • de Groot J.
        Effecct of sectioning the formix on diurnal fluctuation in plasma corticosterone levels in the rat.
        Neuroendocrinology. 1971; 7: 11-18
        • Naar S.
        • Rodgers G.
        • Pandey E.
        ACTH, cortisol and the DST in depressed outpatients.
        in: Proc Soc Biol Psychiatry. 37. 1982: 68-75
        • Nelson W.
        • Orr W.
        • Shane S.
        Occurrence of high concentrations of postdexamethasone cortisol in elderly psychiatric impatients.
        J Clin Psychiatry. 1984; 45: 120-128
        • Nelson W.
        • Orr W.
        • Shane S.
        • Stevenson J.
        Hypothalamic-pituitary-adrenal axis activity and age in major depression.
        J Clin Psychiatry. 1984; 45: 120-131
        • Nemeroff C.
        • Widerlov E.
        • Bisette G.
        • Walleus H.
        • Karlsson I.
        • Eklund K.
        • Kilts C.
        • Loosen P.
        • Vale W.
        Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity depressed patients.
        Science. 1984; 226: 1342-1345
        • Plotsky P.
        • Vale W.
        Hemorrhage-induced secretion of corticotropin-releasing factor-like immunoreactivity into the rat hypophysial portal circulation and its inhibition by glucocorticoids.
        Endocrinology. 1984; 114: 164-169
        • Plotsky P.
        • Otto S.
        • Sapolsky R.
        Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation by delayed glucocorticoid feedback.
        Endocrinology. 1986; 119: 1126-1132
        • Plotsky P.
        • Sawchenko P.
        Hypophysial-portal plasma levels, median eminence content, and immunohistochemical staining of corticotropin-releasing factor, arginine vasopressin, and oxytocin after pharmacological adrenalectomy.
        Endocrinology. 1987; 120: 1361-1369
        • Reul J.
        • Tonnaer J.
        • de Kloet E.
        Neurotrophic ACTH analogue promotes plasticity of Type I corticosteroid receptor in brain of senescent male rats.
        Neurobiol Aging. 1988; 9: 253-260
        • Reus V.
        • Joseph M.
        • Dallman M.
        ACTH levels after the dexamethasone suppression test in depression.
        N Engl J Med. 1982; 306: 238-241
        • Rigter H.
        • Veldhuis H.
        • de Kloet E.
        Spatial orientation and the hippocampal corticosterone receptor systems of old rats: Effects of ACTH4–9 analogue ORG2766.
        Brain Res. 1984; 309: 393-399
        • Risch C.
        • Golshan S.
        • Rapport M.
        • Dupont R.
        • Outenreath R.
        • Gillin J.
        • Janowsky D.
        Neuroendocrine effects of intravenous ovine CRF in affective disorder patients and normal controls.
        Biol Psychiatry. 1988; 23: 755-759
        • Rubinow D.
        • Post R.
        • Savard R.
        • Gold P.
        Cortisol hypersecretion and cognitive impairment in depression.
        Arch Gen Psychiatry. 1984; 41: 279-284
        • Saphier D.
        • Feldman S.
        Effects of septal and hippocampal stimuli on paraventricular neurons.
        Neuroscience. 1987; 20: 749-755
        • Sapolsky R.
        Hypercortisolism among socially subordinate wild baboons originates at the CNS level.
        Arch Gen Psychiatry. 1989; 46: 1047-1051
        • Sapolsky R.
        • Krey L.
        • McEwen B.
        Corticosterone receptors decline in a site-specific manner in the aged rat brain.
        Brain Res. 1983; 289: 235-241
        • Sapolsky R.
        • Krey L.
        • McEwen B.
        Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response.
        in: Proc Natl Acad Sci USA. 81. 1984: 6174-6178
        • Sapolsky R.
        • Krey L.
        • McEwen B.
        Stress down-regulates corticosterone receptors in a site specific manner in the brain.
        Endocrinology. 1984; 114: 287-293
        • Sapolsky R.
        • Krey L.
        • McEwen B.
        • Rainbow T.
        Do vasopressin-related peptides induce hippocampal corticosterone receptors? Implications for aging.
        J Neurosci. 1984; 4: 1479-1486
        • Sapolsky R.
        • Meaney M.
        Postmortem decay in glucocorticoid binding in human and primate brain.
        Brain Res. 1988; 448: 182-186
        • Sapolsky R.
        • McEwen B.
        Why dexamethasone resistance: Two possible neuroendocrine mechanism.
        in: Schatzberg A. Nemeroff C. The Hypothalamic-Pituitary-Adrenal Axis: Physiology, Pathophysiology and Psychiatric Implications. Raven Press, New York1988: 155-165
        • Sapolsky R.
        • Armanini M.
        • Packan D.
        • Tombaugh G.
        Stress and glucocorticoids in aging.
        Endocrinol Metab Clin N Am. 1987; 16: 965-980
        • Sapolsky R.
        • Armanini M.
        • Sutton S.
        • Plotsky P.
        Elevation of hypophysial portal concentrations of adrenocorticotropin secretagogues after fornix transection.
        Endocrinology. 1989; 125: 2881-2887

      80. Sapolsky R, Armanini M, Packan D, Sutton S, Plotsky P (in press): Glucocorticoid feedback inhibition of ACTH-secretagogue release: Relationship to corticopsteroid receptor occupancy in various limbic sites. Neuroendocrinology.

        • Spar J.
        • La Rue A.
        Major depression in the elderly: DSM-III criteria and the dexamethasone suppression test as predictors of treatment response.
        Am J Psychiatry. 1983; 140: 844-849
        • Stokes P.
        • Stoll P.
        • Koslow S.
        • Maas J.
        • Davis J.
        • Swaan A.
        • Robins E.
        Pretreatment DST and hypothalamic-pituitary-adrenocortical function in depressed patients and comparison groups.
        Arch Gen Psychiatry. 1984; 41: 257-263
        • Touitou Y.
        • Sulon J.
        • Bogdan A.
        The adrenocortical hormones, aging and mental conditions:Seasonal and circadian rhythm of plasma 18-OH-11-DOC, total and free cortisol and urinary corticosteroids.
        J Endocrinol. 1983; 96: 53-59
        • Weiner M.
        • Davis B.
        • Mohs R.
        • Davis K.
        Influence of age and relative weight on cortisol suppression in normal subjects.
        Am J Psychiatry. 1987; 144: 646-651
        • West C.
        • Brown H.
        • Simons E.
        • Carter D.
        • Kumagai L.
        • Engelbert E.
        Adrenocortical function and cortisol metabolism in old age.
        J Clin Endocrinol Metab. 1961; 21: 1197-1203
        • Wilson M.
        Effect of hyppocampectomy on dexamethasone suppression of corticosteroid-sensitive stress responses.
        Anat Record. 1975; 181: 511-517
        • Wilson M.
        • Critchlow V.
        Effect of fornix transection or hippocampectomy on rhythmic pituitary-adrenal function in the rat.
        Neuroendocrinology. 1973; 13: 29-35
        • Wilson M.
        • Greer M.
        • Roberts L.
        Hippocampal inhibition of pituitary-adrenocortical function in female rats.
        Brain Res. 1980; 197: 433-438
        • Wynn P.
        • Harwood J.
        • Catt K.
        • Aguilera G.
        Regulation of corticotropin-releasing factor (CRF) receptors in the rat pituitary gland: Effects of adrenalectomy on CRF receptors and corticotroph responses.
        Endocrinology. 1985; 116: 1653-1659
        • Zimmerman M.
        • Coryell W.
        The dexamethasone suppression test in healthy controls.
        Psychoneuroendocrinology. 1987; 12: 245-257

      Article info

      Publication history

      Received in revised form: October 28, 1989
      Received: July 10, 1989

      Footnotes

      ☆Research was made possible by grants to RMS from the Alzheimer's Disease and Related Disorders Association, The Klingenstein Fund, a Presidential Young Investigators Award, and NIH R01 AG06633, and to PMP from NIH R01 DK33093.

      Identification

      DOI: https://doi.org/10.1016/0006-3223(90)90032-W

      Copyright

      © 1990 Published by Elsevier Inc.

      ScienceDirect

      Access this article on ScienceDirect

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX