| 1. |
- Grönbladh, Alfhild, et al.
(författare)
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The impact of nandrolone decanoate and growth hormone on biosynthesis of steroids in rats
- 2013
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Ingår i: Steroids. - : Elsevier. - 0039-128X .- 1878-5867. ; 78:12-13, s. 1192-1199
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) and anabolic androgenic steroids (AAS) are commonly used in sports communities. Several studies have suggested an association between GH and AAS. We have investigated the impact of GH in rats treated with nandrolone decanoate (ND). Male Wistar rats received ND (15 mg/kg) every third day during three weeks and were subsequently treated with recombinant human GH (1.0 IU/kg) for ten consecutive days. Plasma samples were collected and peripheral organs (i.e. heart, liver, testis and thymus) were dissected and weighed. Concentration of thirteen endogenous steroids was measured in the rat plasma samples using high specificity LC-MS/MS methods. Seven steroids were detected and quantified, and concentrations of estrone, testosterone, and androstenedione were significantly different among the groups, while concentrations of pregnenolone, DHEA, 17- hydroxyprogesterone and corticosterone were not altered. Administration of rhGH alone altered the plasma steroid distribution, and the results demonstrated significantly increased concentrations of plasma estrone as well as decreased concentrations of testosterone and androstenedione in the ND-treated rats. Administration of rhGH to ND-pretreated rats did not reverse the alteration of the steroid distribution induced by ND. Administration of ND decreased the weight of the thymus, and addition of rhGH did not reverse this reduction. However, rhGH administration induced an enlargement of thymus. Taken together, the plasma steroid profile differed in the four groups, i.e. controls, AAS, rhGH and the combination of AAS and rhGH treatment.
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| 4. |
- Kiss, Anita, et al.
(författare)
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Synthesis of novel 17-triazolyl-androst-5-en-3-ol epimers via Cu(I)-catalyzed azide-alkyne cycloaddition and their inhibitory effect on 17 alpha-hydroxylase/ C-17,C-20-lyase
- 2018
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X .- 1878-5867. ; 135, s. 79-91
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Tidskriftsartikel (refereegranskat)abstract
- The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of 17 alpha- and 17 beta-azidoandrost-5-en-3 beta-ol epimers (3b and 5b) with different terminal alkynes afforded novel 1,4-substituted triazolyl derivatives (8a-k and 9a-k). For the preparation of 5'-iodo-l',2',3'-triazoles (8m-n and 9m-n), an improved method was developed, directly from steroidal azides and terminal alkynes, in reaction mediated by Cul and IC1 as iodinating agents. Acetolysis and subsequent hydrolysis of 8n and 9n yielded 5'-hydroxy-l',2',3'-triazoles 8o and 9o. The inhibitory effect of 8a-o, 9a-o, 3, and 5 on rat testicular C-17,C-20-lyase was investigated by means of an in vitro radioincubation technique. The results revealed that the C-17 epimers of steroidal triazoles influence the C-17,C-20-lyase effect. Inhibitors were found only in the 17 alpha-triazolyl series (8a-o), whereas in the C-17 azide pair the 17 beta compound (5b) was more potent.
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| 5. |
- Larik, Fayaz Ali, et al.
(författare)
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Synthetic approaches towards the multi target drug spironolactone and its potent analogues/derivatives
- 2017
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X .- 1878-5867. ; 118, s. 76-92
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Forskningsöversikt (refereegranskat)abstract
- Spironolactone is a well-known multi-target drug and is specifically used for the treatment of high blood pressure and heart failure. It is also used for the treatment of edema, cirrhosis of the liver, malignant, pediatric, nephrosis and primary hyperaldosteronism. Spironolactone in association with thiazide diuretics treats hypertension and in association with furosemide treats bronchopulmonary dyspepsia. The therapeutic mechanism of action of spironolactone involves binding to intracellular mineralocorticoids receptors (MRs) in kidney epithelial cells, thereby inhibiting the binding of aldosterone. Since its first synthesis in 1957 there are several synthetic approaches have been reported throughout the years, Synthetic community has devoted efforts to improve the synthesis of spironolactone and to synthesize its analogues and derivatives. This review aims to provide comprehensive insight for the synthetic endeavors devoted towards the synthesis of a versatile drug spironolactone and its analogues/derivatives.
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| 7. |
- Lundqvist, Johan
(författare)
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1α,25-Dihydroxyvitamin D3 inhibits cell growth and NFκB signaling in tamoxifen-resistant breast cancer cells
- 2014
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X .- 1878-5867. ; 85, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- Resistance to antiestrogens is a major clinical problem in current breast cancer treatment and development of new treatment strategies for these tumors is highly prioritized. In this study, we have investigated the effects of 1 alpha,25-dihydroxyvitamin D-3 on the proliferation of tamoxifen-resistant cells. Further, we have investigated on a molecular level the effects of vitamin D on NF kappa B signaling in tamoxifen-resistant breast cancer cells. Parental human breast cancer MCF-7 cells and four tamoxifen-resistant sublines have been used to investigate the effects of 1 alpha,25-dihydroxyvitamin 133 on cell proliferation using a colorimetric method, gene expression using quantitative PCR, protein phosphorylation using Western blot analysis and cellular localization of proteins using immunofluorescence microscopy. We found that 1 alpha,25-dihydroxyvitamin D-3 is able to strongly decrease the growth of both tamoxifen-sensitive and -resistant breast cancer cells and that this antiproliferative effect of 1 alpha,25-dihydroxyvitamin D-3 might be mediated via inhibition of the NF kappa B pathway. We found that 1 alpha,25-dihydroxyvitamin D-3 stimulates the gene expression of IkB, an NM-inhibiting protein, and that cells pretreated with 1 alpha,25-dihydroxyvitamin D-3 have a decreased sensitivity to TNF alpha stimulation. Further, we show that 1 alpha,25-dihydroxyvitamin D-3 treatment strongly decreases the TNF alpha-induced translocation of p65 into the nucleus. This manuscript reports novel findings regarding the effects of 1 alpha,25-dihydroxyvitamin D-3 on NF kappa B signaling in tamoxifen-resistant breast cancer cells and suggests that vitamin D might be interesting for further evaluation as a new strategy to treat antiestrogen-resistant breast cancers. (C) 2014 Elsevier Inc. All rights reserved.
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| 13. |
- Söderberg, Ewa, et al.
(författare)
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Counteraction of early circulatory derangement by administration of low dose steroid treatment at the onset of established endotoxemic shock is not directly mediated by TNF-α and IL-6
- 2012
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X .- 1878-5867. ; 77:11, s. 1101-1106
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Once a septic condition is progressing, administration of steroids in the pro-inflammatory phase of septic shock ought to yield maximal effect on the subsequent, devastating inflammatory response. Recently, a retrospective study showed that early initiation of corticosteroid therapy improved survival in septic shock. We aimed to prospectively evaluate effects of early administrated hydrocortisone therapy on physiologic variables in a porcine model of septic shock.EXPERIMENT:Eight anesthetized pigs were given a continuous infusion of endotoxin during this 6h prospective, randomized, parallel-grouped placebo-controlled experimental study. At the onset of endotoxemic shock, defined as the moment when the mean pulmonary arterial pressure reached the double baseline value, the pigs were either given a single intravenous dose of hydrocortisone (5 mg kg−1) or the corresponding volume of saline.RESULTS:Mean arterial pressure and systemic vascular resistance index were significantly higher (both p<0.05), and heart rate was significantly lower (p<0.05), in the endotoxin+hydrocortisone group as compared to the endotoxin+saline group. Body temperature and blood hemoglobin levels increased significantly in the endotoxin+saline group (both p<0.05). Urinary hydrocortisone increased significantly in both groups (p<0.05). There were no significant differences in the plasma levels of TNF-alpha, IL-6 or nitrite/nitrate between the groups.CONCLUSION:Early treatment with hydrocortisone ameliorates some endotoxin mediated circulatory derangements, fever response and microvascular outflow. Our results suggest that these effects are not directly mediated by the pro-inflammatory cytokines TNF-alpha or IL-6, nor by NO.
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| 15. |
- Thomas, Peter, et al.
(författare)
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Conserved estrogen binding and signaling functions of the G protein-coupled estrogen receptor 1 (GPER) in mammals and fish
- 2010
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Ingår i: Steroids. - Amsterdam : Elsevier. - 0039-128X .- 1878-5867. ; 75:8-9, s. 595-602
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies by several research groups have shown that G protein estrogen receptor-1 (GPER) formerly known as GPR30, mediates 17beta-estradiol (E2) activation of signal transduction pathways in a variety of human cancer cells and displays E2 binding typical of a membrane estrogen receptor. However, the importance of GPER as an estrogen receptor has been questioned by Otto and co-workers. Some of the pitfalls in investigating the functions of recombinant steroid membrane receptors that may explain the negative results of these investigators are discussed. The characteristics of GPER have also been investigated in a teleost fish, Atlantic croaker, where it has been shown to mediate E2 inhibition of oocyte maturation. Investigations on newly discovered homologous proteins from distantly related vertebrate groups are valuable for determining their fundamental, evolutionarily conserved functions. Therefore, the functions of croaker and human GPERs were compared. The comparisons show that croaker and human GPER have very similar estrogen binding characteristics, typical of estrogen membrane receptors, and activate the same estrogen signaling pathways via stimulatory G proteins (Gs) resulting in increased cAMP production. These results suggest that the estrogen binding and estrogen signaling functions of GPER arose early in vertebrate evolution, prior to the divergence of the teleosts from the tetrapods, more than 200 million years ago. The finding that estrogen membrane signaling through GPER has been conserved for such a long period in two distantly related vertebrate groups, mammals and fish, suggests that this is a fundamental function of GPER in vertebrates, and likely its major physiological role.
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| 16. |
- Thomas, Peter, et al.
(författare)
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Progestin, estrogen and androgen G-protein coupled receptors in fish gonads
- 2006
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Ingår i: Steroids. - : Elsevier. - 0039-128X .- 1878-5867. ; 71:4, s. 310-316
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Tidskriftsartikel (refereegranskat)abstract
- The identities of the membrane receptors mediating the majority of rapid, cell surface-initiated, nongenomic (i.e. nonclassical) steroid actions described to date are unclear. Two novel 7-transmembrane spanning proteins, representing two distinct classes of steroid membrane receptors, membrane progestin receptor alpha (mPRalpha) and a membrane estrogen receptor (mER), GPR30, have recently been identified in several vertebrate species. Evidence that both receptors activate G-proteins and function as G-protein coupled receptors (GPCRs) is briefly reviewed. New data on progestin actions on fish gametes suggest a widespread involvement of mPRalpha in oocyte maturation and sperm hyperactivity in this vertebrate group. Information on the second messenger pathways activated upon estrogen binding to a membrane estrogen receptor in croaker gonads and preliminary evidence for the presence of a GPR30-like protein in fish gonads are discussed. Finally, initial characterization of the ligand binding, G-protein activation and molecular size of a membrane androgen receptor (mAR) in croaker ovaries suggests the presence of a third unique steroid receptor in fish gonads that also may function as a GPCR.
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| 17. |
- Bygdeman, M, et al.
(författare)
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Pregnancy termination
- 2000
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Ingår i: Steroids. - 0039-128X. ; 65:10-11, s. 801-805
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Tidskriftsartikel (refereegranskat)
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| 27. |
- Key, T. J., et al.
(författare)
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Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies
- 2015
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X. ; 99, s. 49-55
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study.
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| 31. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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The association between urinary cortisol excretion and cardiovascular risk factors, bone status and quality of life in the population
- 2015
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X. ; 101, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Patients with glucocorticoid excess have increased cardiovascular risk, decreased bone mineral density and impaired quality of life (QoL). The aim of this study was to evaluate the association between urinary cortisol excretion and cardiovascular risk factors, bone status and QoL in the population. We hypothesized that higher cortisol excretion was associated with adverse cardiovascular risk profile, worse skeletal health and QoL. Design, patients and methods: This was a cross-sectional study including a population sample (n = 348), aged 38-77 years. The mean age in women was 64.0 +/- 8.5 years (n = 276) and 60.3 +/- 10.2 years in men (n = 72). The metabolic syndrome, body composition measured with bioimpedance, calcaneal quantitative ultrasound, fractures and QoL evaluated with the Nottingham Health Profile, Psychological General Well-Being (PGWB) and the Short Form 36 (SF-36) were studied. Urinary free cortisol (UFC) was measured using radioimmunoassay. Results: UFC was higher in men (230 +/- 120 nmol/L) compared to women (153 +/- 71; P < 0.001) and decreased with increasing age (P < 0.001). In a regression analysis, after adjustment for gender, age and body mass index, higher UFC was associated with higher fat-free mass (P < 0.01), favourable calcaneal bone measurements (P < 0.05), better general health measured with PGWB (P < 0.01) and SF-36 (P = 0.001) and tended to be negatively associated with the metabolic syndrome (P = 0.07). Conclusion: In contrast to our hypothesis, UFC in the upper physiological range was associated with a favourable cardiovascular risk profile, bone measures and QoL.
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| 32. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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Urinary free cortisol and androgens in the population—Hormone interactions and the relationship with body composition and bone status
- 2016
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X. ; 115, s. 154-159
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Tidskriftsartikel (refereegranskat)abstract
- Objective Abnormal secretion of thyroid hormones, growth hormone, cortisol and androgens influences body composition. We hypothesised that higher cortisol excretion, in combination with higher androgen and IGF-I concentrations, had a synergistic, favourable effect on body mass and bone. Design, patients and methods This was a cross-sectional study on a population sample of 290 women and 93men. The mean age was 65.4±7.2yearsinwomen and 59.7±10.0yearsinmen. Body composition was assessed with bioimpedance, and skeletal health with calcaneal quantitative ultrasound and fracture rate. The influence of urinary free cortisol (UFC), serum DHEAs (women), testosterone (men), free T4andIGF-I on the outcome was studied with regression analyses adjusted for age and body mass index. Results In women, higher concentrations of UFC, DHEAs, IGF-I and lower free T4, were associated with higher fat-free mass. Only a higher UFC concentration was associated with favourable calcaneal measurements. In men, higher testosterone was associated with higher fat-free mass and lower fat mass. Higher IGF-I concentration, but not UFC, was independently associated with higher fat-free mass in men. Interaction analyses did not reveal any additive effects of hormones on body composition or bone in either sex. In both men and women, only age was associated with osteoporotic fractures. Conclusion Serum concentrations of androgens together with IGF-I were positively associated with body composition in both sexes. Urinary cortisol was positively associated with fat-free mass and bone status in women only. Increasing age, but not hormones, was the major determinant of osteoporotic fractures in this population sample. © 2016 Elsevier Inc.
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