Elevated urinary free cortisol in patients with dementia

Maeda, Kiyoshi; Tanimoto, Kenji; Terada, Teruhisa; Shintani, Tetsuya; Kakigi, Tatsuya

doi:10.1016/0197-4580(91)90055-o

Cited by 88 publications

(38 citation statements)

References 16 publications

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“…This contradicts several previous studies that found different cortisol levels between normal and AD [74][75][76][77][78] and between normal and MCI groups [78,79]. Contrarily, it supports the literature that found no correlation between cortisol level and perceived stress in different populations [80][81][82].…”

Section: Discussioncontrasting

confidence: 56%

Systematic Analysis of GWAS Data Reveals Genomic Hotspots for Shared Mechanisms between Neurodegenerative Diseases

Naz¹,

Younesi²,

Hofmann‐Apitius³

2017

J Alzheimers Dis Parkinsonism

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Section: Discussioncontrasting

confidence: 56%

Systematic Analysis of GWAS Data Reveals Genomic Hotspots for Shared Mechanisms between Neurodegenerative Diseases

Naz¹,

Younesi²,

Hofmann‐Apitius³

2017

J Alzheimers Dis Parkinsonism

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“…This evidence suggests that glucocorticoids could play a role in the pathogenesis of Alzheimer's disease (AD), possibly by accelerating hippocampal damage. However, direct evidence from patients with AD is inconclusive, while some studies have found them to be mildly hypercortisolic when compared with a non-demented control group (Davis et al 1986, Maeda et al 1991, Umegaki et al 2000, others have not (Ferrier et al 1988). Furthermore, many patients who are hypercortisolic due to Cushing's syndrome, depression or the administration of synthetic glucocorticoids do not develop AD (Swaab et al 2005).…”

Section: Introductionmentioning

confidence: 99%

The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue

MacKenzie¹,

Dewar²,

Stewart³

et al. 2007

Journal of Endocrinology

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Steroid actions on brain tissue have been implicated in processes such as blood pressure regulation and neurodegeneration, including the progression of Alzheimer's disease (AD). mRNAs from all of the genes required for de novo synthesis from cholesterol of aldosterone and corticosterone (equivalent to cortisol in humans) have been identified in rat brain, together with abundant steroid hormone receptors, but the situation in human brain requires clarification. We used real-time RT-PCR to assess whether transcription of 13 steroid-associated genes occurs in human hippocampus and cerebellum, and to identify whether transcription of these genes is significantly altered in cases of AD. Frozen post-mortem samples of hippocampus and cerebellum from patients with AD (nZ7) and age-matched controls free from neurological disease at the time of death (nZ9) were used. We found all of the genes under investigation to be transcribed within normal and AD hippocampus and cerebellum except for CYP11B1 (11b-hydroxylase), CYP11B2 (aldosterone synthase) and CYP17 (17a-hydroxylase). No significant differences in mRNA levels were observed between the AD tissue and the equivalent control tissue, although significant regional differences in gene transcription were observed between hippocampus and cerebellum in AD and control samples. The absence of key mRNAs from human hippocampus and cerebellum rules out the de novo generation of aldosterone, cortisol or the sex steroids within these regions. However, the pattern of gene expression does suggest that the mineralocorticoid 11-deoxycorticosterone can be generated de novo. There is no evidence of a link between AD and altered steroid biosynthesis within human hippocampus and cerebellum.

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“…Indeed, abnormalities at different levels of the hypothalamic-pituitary-adrenal (HPA) axis have been reported in several diseases such as psychiatric disorders, including depression and mood alteration (Kiraly et al, 1997;Tafet et al, 2001); acquired immunodeficiency syndrome (AIDS) (Corley, 1996;Bhansali et al, 2000;Christeff et al, 2000); multiple sclerosis (Erkut et al, 2002); dementia (Maeda et al, 1991;Polleri et al, 2002), including Alzheimer's disease (AD) (Swaab et al, 1994;O'Brien et al, 1996;Weiner et al, 1997;Giubilei et al, 2001;Rasmuson et al, 2002); and breast cancer outcome (Luecken and Compas, 2002). It has been proposed that disruption of hormonal balance in these diseases leads to increased cortisol production, resulting in elevated concentrations of cortisol in cerebrospinal fluid (Swaab et al, 1994;Erkut et al, 2002), blood (Weiner et al, 1997;Bhansali et al, 2000;Rasmuson et al, 2002), urine (Maeda et al, 1991), and saliva (Giubilei et al, 2001).…”

mentioning

confidence: 99%

Inhibition of Adrenal Cortical Steroid Formation by Procaine Is Mediated by Reduction of the cAMP-Induced 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Messenger Ribonucleic Acid Levels

Xu¹,

Lecanu²,

Han³

et al. 2003

J Pharmacol Exp Ther

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Elevated glucocorticoid levels are associated with many diseases, including age-related depression, hypertension, Alzheimer's disease, and acquired immunodeficiency syndrome. Cortisol-lowering agents could provide useful complementary therapy for these disorders. We examined the effect of procaine and procaine in a pharmaceutical formulation on adrenal cortical steroid formation. Procaine inhibited dibutyryl cyclic AMP (dbcAMP)-induced corticosteroid synthesis by murine Y1 and human H295R adrenal cells in a dose-dependent manner without affecting basal steroid formation. Treatment of rats with the procaine-based formulation reduced circulating corticosterone levels. This steroidogenesis-inhibiting activity of procaine was not observed in Leydig cells, suggesting that the effect was specific to adrenocortical cells. In search of the mechanism underlying this inhibitory effect on cAMP-induced corticosteroidogenesis, procaine was found to affect neither the cAMPdependent protein kinase activity nor key proteins involved in cholesterol transport into mitochondria, cytochrome P450 side chain cleavage enzyme expression, and enzymatic activities associated with cholesterol metabolism to final steroid products. However, procaine reduced in a dose-dependent manner the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCoA) activity and the dbcAMP-induced HMG-CoA reductase mRNA levels by affecting mRNA stability. These data suggest that the inhibitory effect of procaine on cAMP-induced corticosteroid formation is due to the reduced synthesis of cholesterol. This modulatory effect of procaine on HMG-CoA reductase mRNA expression was also seen in dbcAMP-stimulated Hepa1-6 mouse liver hepatoma cells. Taken together, these results suggest that procaine may provide a pharmacological means for the control of hormone-induced HMG-CoA reductase mRNA expression and hypercortisolemia.

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Elevated urinary free cortisol in patients with dementia

Cited by 88 publications

References 16 publications

Systematic Analysis of GWAS Data Reveals Genomic Hotspots for Shared Mechanisms between Neurodegenerative Diseases

Systematic Analysis of GWAS Data Reveals Genomic Hotspots for Shared Mechanisms between Neurodegenerative Diseases

The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue

Inhibition of Adrenal Cortical Steroid Formation by Procaine Is Mediated by Reduction of the cAMP-Induced 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Messenger Ribonucleic Acid Levels

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