Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
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Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
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Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
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Department of Endocrinology, Skaraborg Central Hospital, Skövde, Sweden
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Objective
Sex steroids exert important biological functions within the 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 chromatography–tandem mass spectrometry (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 (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 testosterone (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 testosteronein CSF is derived from circulating testosterone, DHT in CSF is from local conversion from testosterone, while E2 in CSF is from local conversion from 4D in CNS.
Conclusions
We describe the first thoroughly validated highly 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.
Significance statement
In this study, a fully validated highly sensitive mass spectrometric assay for sex steroids was applied to human CSF. The results were used to describe the relative contribution of peripheral circulating sex steroids together with locally transformation of sex steroids to the levels in CSF. The results are of importance to understand the biological processes of the human brain.
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Department of Cardiology, Yanbian University Hospital, Yanji, China
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, 41 ). Piezo 1 is a typical mechanosensitive ion channel protein that links mechanical forces to biological signals ( 42 ). Mechanical stimulation of bone and nerve cells increases the expression of piezo 1, which promotes bone and nerve growth through
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of smooth muscle contraction ( 19 , 20 ). SPP2 has the effects of regulation of vascular calcification and anti-inflammation ( 21 , 22 , 23 ). GC can isolate actin, regulate immune and inflammatory responses, bind fatty acids, and control bone
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.31) 13 −2.57 (1.54) Bone age/chronological age 163 0.83 (0.19) 8 0.87 (0.10) IGF1 SDS (22) 162 −1.13 (1.62) 7 −1.22 (1.98) GH dose at baseline (mg/kg/day) 404 0.044 (0.014) 21 0.040 (0.019) GH-naïve at
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Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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Cardiovascular Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan
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/mL is considered to be adequate for improved musculoskeletal health, the optimal serum level of 25(OH)D for organs other than bone remains debatable. The 2018 Vitamin D Supplementation Guidelines recommended daily supplementation of 400–800 IU vitamin D
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to improve body composition (reduced fat mass, increased lean mass and increased muscle strength), bone mineral density and CV risk markers (increased high-density lipoprotein (HDL) cholesterol and reductions in low-density lipoprotein (LDL
