Altered Steroidome in Women with Multiple Sclerosis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023761%3A_____%2F24%3AN0000035" target="_blank" >RIV/00023761:_____/24:N0000035 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10487887 RIV/00216208:11120/24:43927778 RIV/00216208:11130/24:10487887 RIV/00064173:_____/24:43927778 RIV/00064203:_____/24:10487887

Výsledek na webu

<a href="https://doi.org/10.3390/ijms252212033" target="_blank" >https://doi.org/10.3390/ijms252212033</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms252212033" target="_blank" >10.3390/ijms252212033</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Altered Steroidome in Women with Multiple Sclerosis

Popis výsledku v původním jazyce

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly afflicting young women. Various steroids can influence the onset and development of the disease or, on the contrary, mitigate its course; however, a systematic review of steroidomic changes in MS patients is lacking. Based on the gas chromatography tandem mass spectrometry (GC-MS/MS) platform and, in the case of estradiol, also using immunoassay, this study performed a comprehensive steroidomic analysis in 25 female MS patients aged 39(32, 49) years compared to 15 female age-matched controls aged 38(31, 46) years. A significant trend towards higher ratios of conjugated steroids to their unconjugated counterparts was found in patients, which is of particular interest in terms of the balance between excitatory and inhibitory steroid modulators of ionotropic receptors. Patients showed altered metabolic pathway to cortisol with decreased conversion of pregnenolone to 17-hydroxypregnenolone and 17-hydroxypregnenolone to 17-hydroxyprogesterone and increased conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA), resulting in lower levels of 17-hydroxyprogesterone, as well as indications of impaired conversion of 11-deoxy-steroids to 11β-hydroxy-steroids but reduced conversion of cortisol to cortisone. Due to over-activation of hypothalamic-pituitary-adrenal axis (HPAA), however, cortisol and cortisone levels were higher in patients with indications of depleted cortisol synthesizing enzymes. Patients showed lower conversion of DHEA to androstenedione, androstenedione to testosterone, androstenedione to estradiol in the major pathway, and testosterone to estradiol in the minor pathway for estradiol synthesis at increased conversion of androstenedione to testosterone. They also showed lower conversion of immunoprotective Δ(5) androstanes to their more potent 7α/β-hydroxy metabolites and had lower circulating allopregnanolone and higher ratio 3β-hydroxy-steroids to their neuroprotective 3α-hydroxy-counterparts.

Název v anglickém jazyce

Altered Steroidome in Women with Multiple Sclerosis

Popis výsledku anglicky

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly afflicting young women. Various steroids can influence the onset and development of the disease or, on the contrary, mitigate its course; however, a systematic review of steroidomic changes in MS patients is lacking. Based on the gas chromatography tandem mass spectrometry (GC-MS/MS) platform and, in the case of estradiol, also using immunoassay, this study performed a comprehensive steroidomic analysis in 25 female MS patients aged 39(32, 49) years compared to 15 female age-matched controls aged 38(31, 46) years. A significant trend towards higher ratios of conjugated steroids to their unconjugated counterparts was found in patients, which is of particular interest in terms of the balance between excitatory and inhibitory steroid modulators of ionotropic receptors. Patients showed altered metabolic pathway to cortisol with decreased conversion of pregnenolone to 17-hydroxypregnenolone and 17-hydroxypregnenolone to 17-hydroxyprogesterone and increased conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA), resulting in lower levels of 17-hydroxyprogesterone, as well as indications of impaired conversion of 11-deoxy-steroids to 11β-hydroxy-steroids but reduced conversion of cortisol to cortisone. Due to over-activation of hypothalamic-pituitary-adrenal axis (HPAA), however, cortisol and cortisone levels were higher in patients with indications of depleted cortisol synthesizing enzymes. Patients showed lower conversion of DHEA to androstenedione, androstenedione to testosterone, androstenedione to estradiol in the major pathway, and testosterone to estradiol in the minor pathway for estradiol synthesis at increased conversion of androstenedione to testosterone. They also showed lower conversion of immunoprotective Δ(5) androstanes to their more potent 7α/β-hydroxy metabolites and had lower circulating allopregnanolone and higher ratio 3β-hydroxy-steroids to their neuroprotective 3α-hydroxy-counterparts.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/NU20-04-00450" target="_blank" >NU20-04-00450: Hormonální změny u pacientů s roztroušenou sklerózou</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

International Journal of Molecular Sciences

ISSN

1661-6596

e-ISSN

1422-0067

Svazek periodika

25

Číslo periodika v rámci svazku

22

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

37

Strana od-do

12033

Kód UT WoS článku

001365305500001

EID výsledku v databázi Scopus

2-s2.0-85210304031