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

MacKenzie, S. M. , Dewar, D. , Stewart, W. , Fraser, R., Connell, J. M. C. and Davies, E. (2008) The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue. Journal of Endocrinology, 196(1), pp. 123-130. (doi:10.1677/JOE-07-0427)

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Abstract

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 (n=7) and age-matched controls free from neurological disease at the time of death (n=9) were used. We found all of the genes under investigation to be transcribed within normal and AD hippocampus and cerebellum except for CYP11B1 (11β-hydroxylase), CYP11B2 (aldosterone synthase) and CYP17 (17α-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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dewar, Dr Deborah and Stewart, Dr William and Davies, Professor Eleanor and Connell, Professor John and MacKenzie, Dr Scott and Fraser, Prof Robert
Authors: MacKenzie, S. M., Dewar, D., Stewart, W., Fraser, R., Connell, J. M. C., and Davies, E.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Journal of Endocrinology
Publisher:BioScientifica Ltd.
ISSN:0022-0795
ISSN (Online):1479-6805
Published Online:15 October 2007
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392521Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences
392522Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences