title: Preliminary evidence of altered steroidogenesis in women with Alzheimer's disease: Have the patients "OLDER" adrenal zona reticularis?
abstract: 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.
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: mvankova@endo.cz.
authors.forename: Markéta
authors.initials: M
authors.lastname: Vaňková
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: mhill@endo.cz.
authors.forename: Martin
authors.initials: M
authors.lastname: Hill
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: mvelikova@endo.cz.
authors.forename: Marta
authors.initials: M
authors.lastname: Velíková
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: jvcelak@endo.cz.
authors.forename: Josef
authors.initials: J
authors.lastname: Včelák
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: gvacinova@endo.cz.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Vacínová
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: kdvorakova@endo.cz.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Dvořáková
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: plukasova@endo.cz.
authors.forename: Petra
authors.initials: P
authors.lastname: Lukášová
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: dvejrazkova@endo.cz.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vejražková
authors.affiliation: Department of Neurology, Thomayer's Hospital, Vídeňská 800, Prague 140 59, Czech Republic. Electronic address: robert.rusina@ftn.cz.
authors.forename: Robert
authors.initials: R
authors.lastname: Rusina
authors.affiliation: Faculty of Humanities, Charles University in Prague, Ovocný trh 5, Prague 110 00, Czech Republic. Electronic address: iva.holmerova@gerontocentrum.cz.
authors.forename: Iva
authors.initials: I
authors.lastname: Holmerová
authors.affiliation: Faculty of Humanities, Charles University in Prague, Ovocný trh 5, Prague 110 00, Czech Republic. Electronic address: eva.jarolimova@gerontocentrum.cz.
authors.forename: Eva
authors.initials: E
authors.lastname: Jarolímová
authors.affiliation: Faculty of Humanities, Charles University in Prague, Ovocný trh 5, Prague 110 00, Czech Republic; Third Faculty of Medicine, Charles University in Prague, Ovocný trh 5, Prague 110 00, Czech Republic. Electronic address: h.van@seznam.cz.
authors.forename: Hana
authors.initials: H
authors.lastname: Vaňková
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: rkanceva@endo.cz.
authors.forename: Radmila
authors.initials: R
authors.lastname: Kancheva
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: bbendlova@endo.cz.
authors.forename: Běla
authors.initials: B
authors.lastname: Bendlová
authors.affiliation: Institute of Endocrinology, Národní 8, Prague 116 94, Czech Republic. Electronic address: lstarka@endo.cz.
authors.forename: Luboslav
authors.initials: L
authors.lastname: Stárka
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006728:Hormones / Q000097:blood*; D006801:Humans; D010088:Oxidoreductases / Q000378:metabolism; D011375:Progesterone Reductase / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism; D015385:Zona Reticularis / Q000378:metabolism
chemical_list: D006728:Hormones; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase; D015238:Sulfotransferases; C028152:alcohol sulfotransferase
keywords: Alzheimer’s disease; GC–MS; Multivariate statistics; RIA; Steroid metabolome; Women