Preliminary evidence of altered steroidogenesis in women with Alzheimer's disease: Have the patients "OLDER" adrenal zona reticularis?
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26704533
DOI
10.1016/j.jsbmb.2015.12.011
PII: S0960-0760(15)30155-2
Knihovny.cz E-resources
- Keywords
- Alzheimer’s disease, GC–MS, Multivariate statistics, RIA, Steroid metabolome, Women,
- MeSH
- Alzheimer Disease blood metabolism MeSH
- Hormones blood MeSH
- Humans MeSH
- Oxidoreductases metabolism MeSH
- Gas Chromatography-Mass Spectrometry MeSH
- Progesterone Reductase metabolism MeSH
- Aged MeSH
- Sulfotransferases metabolism MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Zona Reticularis metabolism MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 3 beta-hydroxysteroid dehydrogenase type II MeSH Browser
- 3-oxo-5 beta-steroid delta 4-dehydrogenase MeSH Browser
- alcohol sulfotransferase MeSH Browser
- Hormones MeSH
- Oxidoreductases MeSH
- Progesterone Reductase MeSH
- Sulfotransferases MeSH
- Cytochrome P-450 Enzyme System MeSH
Alzheimer's disease (AD) represents more than half of total dementias. Various factors including altered steroid biosynthesis may participate in its pathophysiology. We investigated how the circulating steroids (measured by GC-MS and RIA) may be altered in the presence of AD. Sixteen women with AD and 22 age- and BMI-corresponding controls aged over 65 years were enrolled in the study. The steroid levels (47 steroids and steroid polar conjugates) and their ratios in AD female patients indicated increased CYP11A1 activity, weakened activity of the CYP17A1C17,20 lyase metabolic step and attenuated sulfotransferase SULT2A1 activity at higher activity of the CYP17A1 17-hydroxylase step. The patients showed diminished HSD3B2 activity for C21 steroids, abated conversion of 17-hydroxyprogesterone to cortisol, and significantly elevated cortisol. The women with AD had also attenuated steroid 7α-hydroxylation forming immunoprotective Δ(5)-C19 steroids, attenuated aromatase activity forming estradiol that induces autoimmunity and a shift from the 3β-hydroxy-5α/β-reduced C19 steroids to their neuroinhibitory and antiinflammatory GABAergic 3α-hydroxy- counterparts and showed higher levels of the 3α-hydroxy-5α/β-reduced C21 steroids and pregnenolone sulfate (improves cognitive abilities but may be both protective and excitotoxic). Our preliminary data indicated functioning of alternative "backdoor" pathway in women with AD showing higher levels of both 5α/β-reduced C21 steroids but reduced levels of both 5α/β-reduced C21 steroids, which implied that the alternative "backdoor" pathway might include both 5α- and 5β-reduced steroids. Our study suggested relationships between AD status in women based on the age of subjects and levels of 10 steroids measured by GC-MS.
Department of Neurology Thomayer's Hospital Vídeňská 800 Prague 140 59 Czech Republic
Faculty of Humanities Charles University Prague Ovocný trh 5 Prague 110 00 Czech Republic
Institute of Endocrinology Národní 8 Prague 116 94 Czech Republic
References provided by Crossref.org
The Role of Steroidomics in the Diagnosis of Alzheimer's Disease and Type 2 Diabetes Mellitus
Steroid Sulfation in Neurodegenerative Diseases
