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- Johansson, Per, 1966, et al.
(författare)
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Mild dementia is associated with increased adrenal secretion of cortisol and precursor sex steroids in women.
- 2011
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Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 75:3, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- Context Sex steroid levels decrease with increasing age, but little is known whether this is of importance for the age-related decline in cognitive function. Design and patients A cross-sectional study of 50 (26 men) consecutive patients under primary evaluation of cognitive impairment (D group) and 18 (9 men) matched healthy controls (C group). Measurements Sex steroid and precursor levels were determined in serum and, when measurable, in cerebrospinal fluid (CSF) using gas chromatography/mass spectroscopy (GC-MS) or liquid chromatography/mass spectroscopy (LC-MS). Sex hormone binding globulin (SHBG) and cortisol concentrations were measured using conventional assays. Results Patients in the D group had higher 24-h urine cortisol levels and increased serum levels of dehydroepiandrosterone (DHEA) and its sulphate ester dihydroepiandrosterone sulphate (DHEAS), androsterone (ADT), and oestrone (E1) and its sulphate ester E1S, compared with the controls. When men and women were analysed separately, increased serum concentrations of E1 and E1S were observed in both D men and D women, whereas increased levels of other sex steroids and cortisol were seen only in D women. Conclusions In both D men and women, serum E1 and E1S levels were increased, whereas other changes were gender specific and only seen in D women. Further studies are needed to determine whether these changes are a cause of, or merely a consequence of, cognitive impairment in elderly subjects.
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- Knutsen Rydberg, Ellen, 1969, et al.
(författare)
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Hypoxia increases LDL oxidation and expression of 15-lipoxygenase-2 in human macrophages
- 2004
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Ingår i: Arterioscler Thromb Vasc Biol. ; 24:11, s. 2040-2045
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Macrophage-mediated oxidation of low-density lipoprotein (LDL) by enzymes, such as the lipoxygenases, is considered of major importance for the formation of oxidized LDL during atherogenesis. Macrophages have been identified in hypoxic areas in atherosclerotic plaques. METHODS AND RESULTS: To investigate the role of hypoxia in macrophage-mediated LDL oxidation, we incubated human monocyte-derived macrophages with LDL under normoxic (21% O2) or hypoxic (0% O2) conditions. The results showed that hypoxic macrophages oxidized LDL to a significantly higher extent than normoxic cells. Interestingly, the mRNA and protein expression of 15-lipoxygenase-2 (15-LOX-2) as well as the activity of this enzyme are elevated in macrophages incubated at hypoxia. Both the unspliced 15-LOX-2 and the spliced variant 15-LOX-2sv-a are found in macrophages. In addition, 15-LOX-2 was identified in carotid plaques in some macrophage-rich areas but was only expressed at low levels in nondiseased arteries. CONCLUSIONS: In summary, these observations show for the first time that 15-LOX-2 is expressed in hypoxic macrophages and in atherosclerotic plaques and suggest that 15-LOX-2 may be one of the factors involved in macrophage-mediated LDL oxidation at hypoxia.
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- Ryberg, Henrik, 1971, et al.
(författare)
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Sex steroid levels in corresponding cerebrospinal fluid and serum samples quantified by mass spectrometry in men.
- 2023
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Ingår i: Endocrine connections. - 2049-3614. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.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.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.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.
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