Altered steroidogenesis in patients with Alzheimer's disease — ASN Events
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  3. Altered steroidogenesis in patients with Alzheimer's disease

Altered steroidogenesis in patients with Alzheimer's disease (#403)

Martin Hill 1 , M. Velíková 1 , M. Vaňková 1
  1. Department of Steroids and Proteofactors, Institute of Endocrinology, Prague, Czech Republic

Introduction: Circulating levels of some steroids are significantly altered in patients with Alzheimer disease (AD).

Objective: The purpose of this study was to compare the steroidogenesis in patients with AD with age- and sex-matched controls.

Material and methods: Serum samples were obtained from 52 women 72.3 (64.0; 76.7) years of age (expressed as median with quartiles) out of whom 22 were controls and 29 men 71.5 (66.5; 76.6) years of age out of whom 11 were controls. The unconjugated steroids were extracted with diethyl ether, partitioned between a mixture of methanol with water and n-pentane and derivatized by methoxylamine hydrochloride and then silylated. The conjugated steroids were hydrolyzed and then processed in the same way as their unconjugated counterparts. Steroids and steroid conjugates were mostly quantified using a single quadrupole GC-MS in selective ion monitoring regime using a column with medium polarity. Some steroids were also quantified by immunoassays. The alterations in individual steroidogenic enzymes or in their groups were assessed from product to precursor ratios using an ANOVA model consisting of factors Gender and Status, and Gender × Status interaction.

Results and discussion: AD patients had increased activity of C17-hydroxylation at reduced C17,20-lyase activity (both catalyzed by CYP17A1) in the Δ5 pathway but increased activity of both steps in the Δ4 pathway. Activities of type 2 3β-hydroxysteroid dehydrogenase, Δ5/Δ4 isomerase (HSD3B2), aromatase (CYP19A1), 5α-reductase (SRD5A) were reduced in AD patients and men with AD showed decreased activity of testicular type 3 17β-hydroxysteroid dehydrogenase (HSD17B3). Alternatively, the AD patients have higher 16α-hydroxylation (CYP3A7) activity.

Conclusion: An increased activity of zona fasciculata at reduced activity of zona reticularis in adrenals and decreased production of neuroexcitatory Δ5-steroids as well as suppressed syntheses of estradiol were found in AD patients of both genders. Reduced conversion of androstenediol to testosterone was recorded in men with AD.

Grants from IGA NT/11513-5, NT/12211-5, NT/13543-4, NT/13890-4, NT/12340-5, NT11277-6 a NT/13814-4 supported this study.