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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materials given at the end of this article). Figure 1 PRISMA flow chart of inclusion of studies. Results from the selected studies on pharmacokinetics, hypogonadal symptoms, virilization, metabolic and anthropometric parameters, bone mineral
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Department of Obstetrics and Gynecology, University of Oulu and Oulu University Hospital, Medical Research Center, PEDEGO Research Unit, Oulu, Finland
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outcome(s), bone density measurements and incidence of osteoporosis, and cardiovascular symptoms and disease. The patients were also asked to report any malignancies, operations, and neurological, psychological, respiratory, gastrointestinal, cutaneous, or
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relative to a normal population or a population with TS.). Height velocity (HV), defined as increment in height per year in centimeters, and bone age (a measure of skeletal maturity) were secondary outcome measures of this study. Data were abstracted by a
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Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Endocrine Laboratory, Amsterdam, Netherlands
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Introduction Parathyroid hormone (PTH) plays a critical role in maintaining adequate serum calcium homeostasis. It increases serum calcium by stimulating bone resorption, promoting phosphate excretion, converting vitamin D to its active form
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China
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Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China
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Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China
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Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China
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reaction ( 10 ), then lead to function changes of osteoblasts and osteoclasts ( 11 , 12 ) and impair bone formation eventually. Moreover, David et al . argued that the formation of AGEs in high glycemic conditions, may contribute to a slower rate of
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Hypoparathyroidism is genetically heterogeneous and characterized by low plasma calcium and parathyroid hormone (PTH) concentrations. X-linked hypoparathyroidism (XLHPT) in two American families is associated with interstitial deletion-insertions involving deletions of chromosome Xq27.1 downstream of SOX3 and insertions of predominantly non-coding DNA from chromosome 2p25.3. These could result in loss, gain, or movement of regulatory elements, which include ultraconserved element uc482, which could alter SOX3 expression. To investigate this, we analysed SOX3 expression in EBV-transformed lymphoblastoid cells from three affected males, three unaffected males, and four carrier females from one XLHPT family. SOX3 expression was similar in all individuals, indicating that the spatiotemporal effect of the interstitial deletion-insertion on SOX3 expression postulated to occur in developing parathyroids did not manifest in lymphoblastoids. Expression of SNTG2, which is duplicated and inserted into the X chromosome, and ATP11C, which is moved telomerically, were also similarly expressed in all individuals. Investigation of male hemizygous (Sox3 −/Y and uc482 −/Y) and female heterozygous (Sox3 +/ − and uc482 +/ −) knockout mice, together with wild-type littermates (male Sox3 +/Y and uc482 +/Y, and female Sox3 +/+ and uc482 +/+), revealed Sox3 −/Y, Sox3 +/ −, uc482 −/Y, and uc482 +/ − mice to have normal plasma biochemistry, compared to their respective wild-type littermates. When challenged with a low calcium diet, all mice had hypocalcaemia, and elevated plasma PTH concentrations and alkaline phosphatase activities, and Sox3 −/Y, Sox3 +/ −, uc482 −/Y, and uc482 +/ − mice had similar plasma biochemistry, compared to wild-type littermates. Thus, these results indicate that absence of Sox3 or uc482 does not cause hypoparathyroidism and that XLHPT likely reflects a more complex mechanism.
Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK
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Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
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Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK
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cell field, owing to their multipotent differentiation capacity, low tumorigenicity and tolerogenic nature for allogenic cell-based therapies. They were initially isolated from the adult bone marrow and have subsequently been harvested from several
Department of Endocrinology, St James’s Hospital, Dublin, Ireland
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Department of Endocrinology, University of Manchester, Manchester, UK
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Department of Paediatric Endocrinology & Diabetes, Newcastle-upon-Tyne Hospitals, Newcastle upon Tyne, UK
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Endocrine Research Group, Institute of Genetic Medicine, University of Newcastle-upon-Tyne, Newcastle upon Tyne, UK
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interquartile ranges. Pre- and post-treatment parameters were compared using the Mann–Whitney U -test. Results Longitudinal data detailing pubertal staging, laboratory parameters and bone mineral density are shown in Table 2 . All patients completed
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Division of Musculoskeletal Section, Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
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Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
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School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
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Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
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Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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manifestations ( 2 ). Previous studies have identified that FL may be associated with bone mineral density (BMD) and osteoporosis. However, these associations have been inconsistent. Some studies have demonstrated that FL negatively affects BMD and increases
