Sex steroid levels in corresponding cerebrospinal fluid and serum samples quantified by mass spectrometry in men

Henrik Ryberg, Anna-Karin Norlén, Andreas Landin, Per Johansson, Zeinab Salman, Anders Wallin, Johan Svensson, Claes Ohlsson

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: Sex steroids exert important biological functions within the central nervous system (CNS), but the underlying mechanisms are poorly understood. The contribution of circulating sex steroids to the levels in CNS tissue and cerebrospinal fluid (CSF) has been sparsely investigated in human and with inconclusive results. This could partly be due to lack of sensitive validated assays. To address this, we validated a gas chromatographic-mass spectrometric (GC-MS/MS) assay for quantification of sex steroid hormones/precursors in CSF.

METHODS: GC-MS/MS quantification of dihydrotestosterone (DHT, CSF lower limit of quantification, 1.5 pg/mL), testosterone (T, 4.9), estrone (E1, 0.88), estradiol (E2, 0.25), dehydroepiandrosterone (DHEA, 38.4), androstenedione (4D, 22.3) and progesterone (P, 4.2) in CSF, and corresponding serum samples from 47 men.

RESULTS: Analyses of CSF revealed that DHEA was the major sex steroid (73.5±31.7 pg/mL) followed by 4D (61.4±29.6 pg/mL) and T (49.5±18.9 pg/mL). The CSF levels of DHT, E2 and E1 were substantially lower, and P was in general not detectable in CSF. For all sex steroids except E2, strong associations between corresponding CSF and serum levels were observed. We propose that T in CSF is derived from circulating T, DHT in CSF is from local conversion from T, while E2 in CSF is from local conversion from 4D in CNS.

CONCLUSIONS: We describe the first thoroughly validated high-sensitive mass spectrometric assay for a broad sex steroid hormone panel suitable for human CSF. This assay constitutes a new tool for investigation of the role of sex steroid hormones in the human CNS.

Original languageEnglish
JournalEndocrine Connections
Volume13
Issue number1
Early online date2023 Nov 1
DOIs
Publication statusPublished - 2023
Externally publishedYes

Subject classification (UKÄ)

  • Clinical Medicine
  • Endocrinology and Diabetes
  • Analytical Chemistry
  • Medicinal Chemistry
  • Biomedical Laboratory Science/Technology

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