The transcription of steroidogenic genes in the human cerebellum and hippocampus: a comparative survey of normal and Alzheimer's tissue.
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 (11beta-hydroxylase), CYP11B2 (aldosterone synthase) and CYP17 (17alpha-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.
MacKenzie
Scott M
SM
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Dewar
Deborah
D
Stewart
William
W
Fraser
Robert
R
Connell
John M C
JM
Davies
Eleanor
E
D000368:Aged; D000369:Aged, 80 and over; D000450:Aldosterone / Q000096:biosynthesis / Q000235:genetics; D000544:Alzheimer Disease / Q000378:metabolism*; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism*; D015925:Cryopreservation; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D015870:Gene Expression; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013256:Steroids / Q000096:biosynthesis*; D014158:Transcription, Genetic
D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D013256:Steroids; D000450:Aldosterone; D013254:Steroid 17-alpha-Hydroxylase; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D006854:Hydrocortisone