The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
R N Mcelhaney - One of the best experts on this subject based on the ideXlab platform.
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Comparative differential scanning calorimetric and FTIR and 31P-NMR spectroscopic studies of the effects of cholesterol and Androstenol on the thermotropic phase behavior and organization of phosphatidylcholine bilayers.
Biophysical journal, 1994Co-Authors: T P Mcmullen, R N Lewis, R N McelhaneyAbstract:We have investigated the comparative effects of the incorporation of increasing quantities of Androstenol and cholesterol on the thermotropic phase behavior of aqueous dispersions of members of a homologous series of linear saturated diacyl PCs1 using high sensitivity DSC. We have also employed FTIR and 31P-NMR spectroscopy to study the comparative effects of Androstenol and cholesterol incorporation on the organization of the host PC bilayer in both the gel and liquid-crystalline states. The effects of Androstenol and cholesterol incorporation on the thermotropic phase behavior of shorter chain PCs like 14:0 PC are generally similar but not identical. The incorporation of either sterol progressively decreases the temperature and enthalpy, but not the cooperativity, of the pretransition and completely abolishes it at sterol concentrations above 5 mol%. Moreover, at sterol concentrations of 1 to 20-25 mol%, both Androstenol and cholesterol incorporation produce DSC endotherms consisting of superimposed sharp and broad components, the former due to the hydrocarbon chain melting of sterol-poor and the latter to the melting of sterol-rich 14:0 PC domains. The temperature and cooperativity of the sharp component are reduced slightly with increasing concentration of Androstenol or cholesterol, and the enthalpy of the sharp component decreases progressively and becomes zero at 20-25 mol% sterol. As well, at cholesterol or Androstenol concentrations above 20-25 mol%, the enthalpy of the broad component also decreases linearly with increasing sterol incorporation and becomes zero at sterol levels of about 50 mol%. However, whereas cholesterol incorporation progressively increases the temperature of the broad component of the DSC endotherm, Androstenol incorporation decreases the temperature of this component. In contrast, the effects of Androstenol and cholesterol incorporation on the thermotropic phase behavior of the intermediate and longer chain PCs studied here are considerably different. Although the incorporation of cholesterol increases the main phase transition temperature of 16:0 PC slightly and decreases the phase transition of 18:0 PC and 21:0 PC, Androstenol incorporation decreases the main phase transition temperatures of all three PCs rather markedly. Moreover, Androstenol is less effective in reducing the enthalpy and cooperativity of the broad component of the DSC endotherm of 16:0 PC and especially 18:0 PC bilayers in comparison to cholesterol. Androstenol incorporation (> 5 mol%) also results in the appearance of a second, low temperature endotherm in the DSC traces of the intermediate and longer chain PC dispersions that is not observed in similar cholesterol/PC dispersions. FTIR and 31P-NMR results suggest that this endotherm arises from a temperature-induced dissolution of Androstenol in the gel phase PC bilayers. This second endotherm occurs at lower Androstenol concentrations and increases in area at a given Androstenol level as the chain length of the host PC bilayer increases. We ascribe the increasing immiscibility of Androstenol in both the gel and liquid-crystalline states of PC bilayers of increasing thickness to an increasing degree of hydrophobic mismatch between the Androstenol molecule and the host phospholipid bilayer.
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Comparative differential scanning calorimetric and FTIR and 31P-NMR spectroscopic studies of the effects of cholesterol and Androstenol on the thermotropic phase behavior and organization of phosphatidylcholine bilayers
Biophysical Journal, 1994Co-Authors: T P Mcmullen, R N Lewis, R N McelhaneyAbstract:We have investigated the comparative effects of the incorporation of increasing quantities of Androstenol and cholesterol on the thermotropic phase behavior of aqueous dispersions of members of a homologous series of linear saturated diacyl PCs1 using high sensitivity DSC. We have also employed FTIR and 31P-NMR spectroscopy to study the comparative effects of Androstenol and cholesterol incorporation on the organization of the host PC bilayer in both the gel and liquid-crystalline states. The effects of Androstenol and cholesterol incorporation on the thermotropic phase behavior of shorter chain PCs like 14:0 PC are generally similar but not identical. The incorporation of either sterol progressively decreases the temperature and enthalpy, but not the cooperativity, of the pretransition and completely abolishes it at sterol concentrations above 5 mol%. Moreover, at sterol concentrations of 1 to 20–25 mol%, both Androstenol and cholesterol incorporation produce DSC endotherms consisting of superimposed sharp and broad components, the former due to the hydrocarbon chain melting of sterol-poor and the latter to the melting of sterol-rich 14:0 PC domains. The temperature and cooperativity of the sharp component are reduced slightly with increasing concentration of Androstenol or cholesterol, and the enthalpy of the sharp component decreases progressively and becomes zero at 20–25 mol% sterol. As well, at cholesterol or Androstenol concentrations above 20–25 mol%, the enthalpy of the broad component also decreases linearly with increasing sterol incorporation and becomes zero at sterol levels of about 50 mol%. However, whereas cholesterol incorporation progressively increases the temperature of the broad component of the DSC endotherm, Androstenol incorporation decreases the temperature of this component. In contrast, the effects of Androstenol and cholesterol incorporation on the thermotropic phase behavior of the intermediate and longer chain PCs studied here are considerably different. Although the incorporation of cholesterol increases the main phase transition temperature of 16:0 PC slightly and decreases the phase transition of 18:0 PC and 21:0 PC, Androstenol incorporation decreases the main phase transition temperatures of all three PCs rather markedly. Moreover, Androstenol is less effective in reducing the enthalpy and cooperativity of the broad component of the DSC endotherm of 16:0 PC and especially 18:0 PC bilayers in comparison to cholesterol. Androstenol incorporation (> 5 mol%) also results in the appearance of a second, low temperature endotherm in the DSC traces of the intermediate and longer chain PC dispersions that is not observed in similar cholesterol/PC dispersions.(ABSTRACT TRUNCATED AT 400 WORDS)
T P Mcmullen - One of the best experts on this subject based on the ideXlab platform.
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Comparative differential scanning calorimetric and FTIR and 31P-NMR spectroscopic studies of the effects of cholesterol and Androstenol on the thermotropic phase behavior and organization of phosphatidylcholine bilayers.
Biophysical journal, 1994Co-Authors: T P Mcmullen, R N Lewis, R N McelhaneyAbstract:We have investigated the comparative effects of the incorporation of increasing quantities of Androstenol and cholesterol on the thermotropic phase behavior of aqueous dispersions of members of a homologous series of linear saturated diacyl PCs1 using high sensitivity DSC. We have also employed FTIR and 31P-NMR spectroscopy to study the comparative effects of Androstenol and cholesterol incorporation on the organization of the host PC bilayer in both the gel and liquid-crystalline states. The effects of Androstenol and cholesterol incorporation on the thermotropic phase behavior of shorter chain PCs like 14:0 PC are generally similar but not identical. The incorporation of either sterol progressively decreases the temperature and enthalpy, but not the cooperativity, of the pretransition and completely abolishes it at sterol concentrations above 5 mol%. Moreover, at sterol concentrations of 1 to 20-25 mol%, both Androstenol and cholesterol incorporation produce DSC endotherms consisting of superimposed sharp and broad components, the former due to the hydrocarbon chain melting of sterol-poor and the latter to the melting of sterol-rich 14:0 PC domains. The temperature and cooperativity of the sharp component are reduced slightly with increasing concentration of Androstenol or cholesterol, and the enthalpy of the sharp component decreases progressively and becomes zero at 20-25 mol% sterol. As well, at cholesterol or Androstenol concentrations above 20-25 mol%, the enthalpy of the broad component also decreases linearly with increasing sterol incorporation and becomes zero at sterol levels of about 50 mol%. However, whereas cholesterol incorporation progressively increases the temperature of the broad component of the DSC endotherm, Androstenol incorporation decreases the temperature of this component. In contrast, the effects of Androstenol and cholesterol incorporation on the thermotropic phase behavior of the intermediate and longer chain PCs studied here are considerably different. Although the incorporation of cholesterol increases the main phase transition temperature of 16:0 PC slightly and decreases the phase transition of 18:0 PC and 21:0 PC, Androstenol incorporation decreases the main phase transition temperatures of all three PCs rather markedly. Moreover, Androstenol is less effective in reducing the enthalpy and cooperativity of the broad component of the DSC endotherm of 16:0 PC and especially 18:0 PC bilayers in comparison to cholesterol. Androstenol incorporation (> 5 mol%) also results in the appearance of a second, low temperature endotherm in the DSC traces of the intermediate and longer chain PC dispersions that is not observed in similar cholesterol/PC dispersions. FTIR and 31P-NMR results suggest that this endotherm arises from a temperature-induced dissolution of Androstenol in the gel phase PC bilayers. This second endotherm occurs at lower Androstenol concentrations and increases in area at a given Androstenol level as the chain length of the host PC bilayer increases. We ascribe the increasing immiscibility of Androstenol in both the gel and liquid-crystalline states of PC bilayers of increasing thickness to an increasing degree of hydrophobic mismatch between the Androstenol molecule and the host phospholipid bilayer.
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Comparative differential scanning calorimetric and FTIR and 31P-NMR spectroscopic studies of the effects of cholesterol and Androstenol on the thermotropic phase behavior and organization of phosphatidylcholine bilayers
Biophysical Journal, 1994Co-Authors: T P Mcmullen, R N Lewis, R N McelhaneyAbstract:We have investigated the comparative effects of the incorporation of increasing quantities of Androstenol and cholesterol on the thermotropic phase behavior of aqueous dispersions of members of a homologous series of linear saturated diacyl PCs1 using high sensitivity DSC. We have also employed FTIR and 31P-NMR spectroscopy to study the comparative effects of Androstenol and cholesterol incorporation on the organization of the host PC bilayer in both the gel and liquid-crystalline states. The effects of Androstenol and cholesterol incorporation on the thermotropic phase behavior of shorter chain PCs like 14:0 PC are generally similar but not identical. The incorporation of either sterol progressively decreases the temperature and enthalpy, but not the cooperativity, of the pretransition and completely abolishes it at sterol concentrations above 5 mol%. Moreover, at sterol concentrations of 1 to 20–25 mol%, both Androstenol and cholesterol incorporation produce DSC endotherms consisting of superimposed sharp and broad components, the former due to the hydrocarbon chain melting of sterol-poor and the latter to the melting of sterol-rich 14:0 PC domains. The temperature and cooperativity of the sharp component are reduced slightly with increasing concentration of Androstenol or cholesterol, and the enthalpy of the sharp component decreases progressively and becomes zero at 20–25 mol% sterol. As well, at cholesterol or Androstenol concentrations above 20–25 mol%, the enthalpy of the broad component also decreases linearly with increasing sterol incorporation and becomes zero at sterol levels of about 50 mol%. However, whereas cholesterol incorporation progressively increases the temperature of the broad component of the DSC endotherm, Androstenol incorporation decreases the temperature of this component. In contrast, the effects of Androstenol and cholesterol incorporation on the thermotropic phase behavior of the intermediate and longer chain PCs studied here are considerably different. Although the incorporation of cholesterol increases the main phase transition temperature of 16:0 PC slightly and decreases the phase transition of 18:0 PC and 21:0 PC, Androstenol incorporation decreases the main phase transition temperatures of all three PCs rather markedly. Moreover, Androstenol is less effective in reducing the enthalpy and cooperativity of the broad component of the DSC endotherm of 16:0 PC and especially 18:0 PC bilayers in comparison to cholesterol. Androstenol incorporation (> 5 mol%) also results in the appearance of a second, low temperature endotherm in the DSC traces of the intermediate and longer chain PC dispersions that is not observed in similar cholesterol/PC dispersions.(ABSTRACT TRUNCATED AT 400 WORDS)
Hans Berglund - One of the best experts on this subject based on the ideXlab platform.
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Activations and deactivations with Androstenol and OO.
2013Co-Authors: Ivanka Savic, Hans BerglundAbstract:Upper: Activation and deactivation with Androstenol and OO. Activation (left) and deactivation (right) detected during smelling of Androstenol, and odors (OO). The OO cluster is located in the amygdala and piriform cortex. Lower: Difference between activations with Androstenol and odors (OO). The Frontal lobe clusters in the Androstenol – OO contrast were not significant. Clusters calculated at P = 0.01, corrected P
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Individual Z-values in the activated clusters.
2013Co-Authors: Ivanka Savic, Hans BerglundAbstract:Graphical presentation of individual Z-values from Talairach's co-ordinate 4 0 -18 (peak activation in the hypothalamus cluster derived from Androstenol – Air, and the Talairach's coordinates 18 -10 -4 and -22 2 -8 (peak activations in the right and left amygdala+piriform cortex clusters derived from OO - Air. The individual values were obtained from the respective peak co-ordinate by lowering the uncorrected threshold to P = 0.1, which allowed retrieval of the respective Z-values although they were far below the significance level for the respective contrast (P = 0.01, corrected p
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Androstenol--a steroid derived odor activates the hypothalamus in women.
PloS one, 2010Co-Authors: Ivanka Savic, Hans BerglundAbstract:Background Whether pheromone signaling exists in humans is still a matter of intense discussion. In the present study we tested if smelling of Androstenol, a steroid produced by the human body and reported to affect human behavior, may elicit cerebral activation. A further issue was to evaluate whether the pattern of activation resembles the pattern of common odors. Methodology PET measurements of regional cerebral blood flow (rCBF) were conducted in 16 healthy heterosexual women during passive smelling of Androstenol, four ordinary odors (OO), and odorless air (the base line condition). Principal findings Smelling Androstenol caused activation of a portion of the hypothalamus, which according to animal data mediates the pheromone triggered mating behavior. Smelling of OO, on the other hand, engaged only the classical olfactory regions (the piriform cortex, lateral amygdala, anterior insular and anterior cingulate cortex). Conclusions The observed pattern of activation is very similar to the pattern previously detected with 4,16-androstadien-3-one in heterosexual females. It suggests that several compounds released by human body may activate cerebral networks involved in human reproduction.
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Androstenol – a Steroid Derived Odor Activates the Hypothalamus in Women
2009Co-Authors: Ivanka Savic, Hans BerglundAbstract:Background: Whether pheromone signaling exists in humans is still a matter of intense discussion. In the present study we tested if smelling of Androstenol, a steroid produced by the human body and reported to affect human behavior, may elicit cerebral activation. A further issue was to evaluate whether the pattern of activation resembles the pattern of common odors. Methodology: PET measurements of regional cerebral blood flow (rCBF) were conducted in 16 healthy heterosexual women during passive smelling of Androstenol, four ordinary odors (OO), and odorless air (the base line condition). Principal findings: Smelling Androstenol caused activation of a portion of the hypothalamus, which according to animal data mediates the pheromone triggered mating behavior. Smelling of OO, on the other hand, engaged only the classical olfactory regions (the piriform cortex, lateral amygdala, anterior insular and anterior cingulate cortex). Conclusions: The observed pattern of activation is very similar to the pattern previously detected with 4,16-androstadien-3one in heterosexual females. It suggests that several compounds released by human body may activate cerebral networks involved in human reproduction
Fukuko Kimura - One of the best experts on this subject based on the ideXlab platform.
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Effects of 5α -Androst-16-en-3α -ol on the Pulsatile Secretion of Luteinizing Hormone in Human Females
Chemical senses, 2000Co-Authors: Kazuyuki Shinohara, Masayo Morofushi, Tosihya Funabashi, Dai Mitsushima, Fukuko KimuraAbstract:We examined the effects of 5α -androst-16-en-3α -ol (3α -Androstenol) on pulsatile luteinizing hormone (LH) secretion in human females. The frequency of the LH pulse in the follicular phase was decreased by exposing the women to 3α -Androstenol.
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Positive Relationship between Menstrual Synchrony and Ability to Smell 5α-Androst-16-en-3α-ol
Chemical senses, 2000Co-Authors: Masayo Morofushi, Kazuyuki Shinohara, Toshiya Funabashi, Fukuko KimuraAbstract:To explore the possibility that compounds which were identified as pheromones in experimental animals mediate human menstrual synchrony, we examined the relationship between menstrual synchrony and the ability to smell putative pheromones, 5α -androst-16-en-3α -ol (3α -Androstenol) and 5α -androst-16-en-3-one (5α -androstenone). When we examined menstrual synchrony among 64 women living together in a college dormitory, we found that 24 (38%) of them became synchronized with room-mates in 3 months. Afterwards, dilution series of 3α -Androstenol and 5α -androstenone and the control odorant (pyridine) were presented to the 64 women and sensitivity to the odors was compared between synchronized and non-synchronized women. No difference was found between the two groups of women in the detection threshold for pyridine, indicating that general olfactory ability did not differ between them. The detection threshold for 3α -Androstenol of synchronized women was significantly lower than that of non-synchronized women, but no difference in the threshold for 5α -androstenone was found between synchronized and non-synchronized women. These results indicate that the women who showed menstrual synchrony had a higher sensitivity to 3α -Androstenol but not necessarily to 5α -androstenone.
Paavo Honkakoski - One of the best experts on this subject based on the ideXlab platform.
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Dual action of oestrogens on the mouse constitutive androstane receptor
Biochemical Journal, 2003Co-Authors: Mika Reinisalo, Johanna Jyrkkärinne, Janne Mäkinen, Kaisa Niemi, Hinfan Chung, Pirkko Viitala, Olavi Pelkonen, Paavo HonkakoskiAbstract:mCAR (mouse constitutive androstane receptor; NR1I3) controls the expression of cytochrome P450 as well as other enzymes involved in drug and steroid metabolism. The high basal activity of mCAR can be modulated by inhibitory steroids related to Androstenol and by activating xenobiotic chemicals such as 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene and chlorpromazine. The ability of oestrogens and some other xenobiotics to activate mCAR is not clear. In the present study, co-transfection assays in HEK-293 cells indicated that oestrogens varied in their efficacy to activate mCAR, depending on variation at the steroid D-ring and position of hydroxy groups. In general, oestrogens were weaker activators of mCAR than 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene and chlorpromazine. Also, the induction of CYP2B10 mRNA by oestrogens was less pronounced in mouse primary hepatocytes. Yeast two-hybrid assays indicated that, unlike Androstenol and the established activators, oestrogens attracted both nuclear receptor co-repressors and co-activators to the mCAR ligand-binding domain, thus limiting the extent of mCAR activation. This novel dual action is not limited to oestrogens, but is shared by some xenobiotic CYP2B inducers such as clotrimazole and methoxychlor. These findings offer an alternative explanation for the recently suggested nuclear activation step of mCAR.
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Molecular determinants of steroid inhibition for the mouse constitutive androstane receptor.
Journal of Medicinal Chemistry, 2003Co-Authors: Johanna Jyrkkärinne, Janne Mäkinen, Jukka Gynther, And Antti Poso, Heidi Savolainen, Paavo HonkakoskiAbstract:The constitutive androstane receptor (CAR) regulates drug and steroid metabolism through binding to cytochrome P450 2B, 2C, and 3A gene enhancers. Uniquely among nuclear receptors, mouse CAR (mCAR) can be suppressed by Androstenol and activated by structurally diverse drugs, pesticides, and environmental pollutants. To gain insight into presently ill-defined structural requirements of mCAR ligands, we employed a mCAR inhibition assay in mammalian HEK293 cells to create a QSAR model that could well predict the inhibition by three unknown steroids. Two novel mCAR inhibitors were thus identified. Yeast two-hybrid assays indicated that steroids inhibit mCAR primarily by promoting association of mCAR with the corepressor NCoR, with only minor contribution from other mechanisms. Analysis of chimeric and mutant mCAR constructs suggested that Androstenol sensitivity is controlled by residues between amino acids 201−263 (helices 5−7) and it does not depend on the residue 350 within helix 12, as previously suggested.
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Molecular determinants of steroid inhibition for the mouse constitutive androstane receptor.
Journal of Medicinal Chemistry, 2003Co-Authors: Johanna Jyrkkärinne, Janne Mäkinen, Jukka Gynther, And Antti Poso, Heidi Savolainen, Paavo HonkakoskiAbstract:The constitutive androstane receptor (CAR) regulates drug and steroid metabolism through binding to cytochrome P450 2B, 2C, and 3A gene enhancers. Uniquely among nuclear receptors, mouse CAR (mCAR) can be suppressed by Androstenol and activated by structurally diverse drugs, pesticides, and environmental pollutants. To gain insight into presently ill-defined structural requirements of mCAR ligands, we employed a mCAR inhibition assay in mammalian HEK293 cells to create a QSAR model that could well predict the inhibition by three unknown steroids. Two novel mCAR inhibitors were thus identified. Yeast two-hybrid assays indicated that steroids inhibit mCAR primarily by promoting association of mCAR with the corepressor NCoR, with only minor contribution from other mechanisms. Analysis of chimeric and mutant mCAR constructs suggested that Androstenol sensitivity is controlled by residues between amino acids 201−263 (helices 5−7) and it does not depend on the residue 350 within helix 12, as previously suggested.