The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
Doodipala Samba Reddy - One of the best experts on this subject based on the ideXlab platform.
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the testosterone derived neurosteroid Androstanediol is a positive allosteric modulator of gabaa receptors
Journal of Pharmacology and Experimental Therapeutics, 2010Co-Authors: Doodipala Samba Reddy, Kuihuan JianAbstract:Testosterone modulates seizure susceptibility, but the underlying mechanisms are obscure. Recently, we demonstrated that testosterone affects seizure activity via its conversion to neurosteroids in the brain. Androstanediol (5α-androstan-3α,17β-diol) is an endogenous neurosteroid synthesized from testosterone. However, the molecular mechanism underlying the seizure protection activity of Androstanediol remains unclear. Here, we show that Androstanediol has positive allosteric activity as a GABAA receptor modulator. In whole-cell recordings from acutely dissociated hippocampus CA1 pyramidal cells, Androstanediol (but not its 3β-epimer) produced a concentration-dependent enhancement of GABA-activated currents (EC50 of 5 μM). At 1 μM, Androstanediol produced a 50% potentiation of GABA responses. In the absence of GABA, Androstanediol has moderate direct effects on GABAA receptor-mediated currents at high concentrations. Systemic doses of Androstanediol (5–100 mg/kg), but not its 3β-epimer, caused dose-dependent suppression of behavioral and electrographic seizures in mouse hippocampus kindling, which is a model of temporal lobe epilepsy. The ED50 value for antiseizure effects of Androstanediol was 50 mg/kg, which did not produce sedation/motor toxicity. At high (2× ED50) doses, Androstanediol produced complete seizure protection that lasted for up to 3 h after injection. The estimated plasma concentrations of Androstanediol producing 50% seizure protection in the kindling model (10.6 μM) are within the range of concentrations that modulate GABAA receptors. These studies suggest that Androstanediol could be a neurosteroid mediator of testosterone actions on neuronal excitability and seizure susceptibility via its activity as a GABAA receptor modulator and that Androstanediol may play a key role in men with epilepsy, especially during the age-related decline in androgen levels.
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a high performance liquid chromatography tandem mass spectrometry assay of the androgenic neurosteroid 3α Androstanediol 5α androstane 3α 17β diol in plasma
Steroids, 2005Co-Authors: Doodipala Samba Reddy, Lata Venkatarangan, Benjamin Chien, Kumar RamuAbstract:Abstract The testosterone metabolite 3α-Androstanediol (5α-androstane-3α,17-diol) is a potential GABA A receptor-modulating neurosteroid with anticonvulsant properties and hence could act as a key neuromodulator in the central nervous system. However, there is no specific and sensitive assay for quantitative determination of the androgenic neurosteroid 3α-Androstanediol in biological samples. We have established a liquid chromatography–tandem mass spectrometry (LC–MS–MS) assay to measure 3α-Androstanediol in rat plasma. Standard 3α-Androstanediol added to rat plasma has been successfully analysed with excellent linearity, specificity, sensitivity, and reproducibility. The sensitivity of the method was
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A high-performance liquid chromatography–tandem mass spectrometry assay of the androgenic neurosteroid 3α-Androstanediol (5α-androstane-3α,17β-diol) in plasma
Steroids, 2005Co-Authors: Doodipala Samba Reddy, Lata Venkatarangan, Benjamin Chien, Kumar RamuAbstract:Abstract The testosterone metabolite 3α-Androstanediol (5α-androstane-3α,17-diol) is a potential GABA A receptor-modulating neurosteroid with anticonvulsant properties and hence could act as a key neuromodulator in the central nervous system. However, there is no specific and sensitive assay for quantitative determination of the androgenic neurosteroid 3α-Androstanediol in biological samples. We have established a liquid chromatography–tandem mass spectrometry (LC–MS–MS) assay to measure 3α-Androstanediol in rat plasma. Standard 3α-Androstanediol added to rat plasma has been successfully analysed with excellent linearity, specificity, sensitivity, and reproducibility. The sensitivity of the method was
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anticonvulsant activity of the testosterone derived neurosteroid 3α Androstanediol
Neuroreport, 2004Co-Authors: Doodipala Samba ReddyAbstract:: 3alpha-Androstanediol is synthesized from testosterone in peripheral tissues and in the brain, but the clinical importance of this neurosteroid remains unclear. This study evaluated the effects of 3alpha-Androstanediol on seizure susceptibility in mouse models of epilepsy. 3alpha-Androstanediol protected mice against seizures induced by GABAA receptor antagonists pentylenetetrazol, picrotoxin, and beta-carboline ester in a dose-dependent fashion. However, 3alpha-Androstanediol was inactive against seizures induced by glutamate receptor agonists kainic acid, NMDA and 4-aminopyridine. Pretreatment with the androgen receptor antagonist flutamide had no effect on seizure protection by 3alpha-Androstanediol. These results suggest that 3alpha-Androstanediol has powerful anticonvulsant activity that occurs largely through non-genomic mechanisms. Testosterone-derived 3alpha-Androstanediol might be an endogenous protective neurosteroid in the brain.
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testosterone modulation of seizure susceptibility is mediated by neurosteroids 3α Androstanediol and 17β estradiol
Neuroscience, 2004Co-Authors: Doodipala Samba ReddyAbstract:Abstract Testosterone modulates seizure susceptibility in animals and humans, but the underlying mechanisms are obscure. Here, testosterone modulation of seizure susceptibility is hypothesized to occur through its conversion to neurosteroids with “anticonvulsant” and “proconvulsant” actions, and hence the net effect of testosterone on neural excitability and seizure activity depends on the levels of distinct testosterone metabolites. Testosterone undergoes metabolism to neurosteroids via two distinct pathways. Aromatization of the A-ring converts testosterone into 17β-estradiol. Reduction of testosterone by 5α-reductase generates 5α-dihydrotestosterone (DHT), which is then converted to 3α-Androstanediol (3α-Diol), a powerful GABA A receptor-modulating neurosteroid with anticonvulsant properties. Systemic doses of testosterone decreased seizure threshold in rats and increased the incidence and severity of pentylenetetrazol (PTZ)-induced seizures in mice. These proconvulsant effects of testosterone were associated with increases in plasma 17β-estradiol and 3α-Diol concentrations. Pretreatment with letrozole, an aromatase inhibitor that blocks the conversion of testosterone to 17β-estradiol, significantly inhibited testosterone-induced exacerbation of seizures. The 5α-reductase inhibitor finasteride significantly reduced 3α-Diol levels and also blocked letrozole's ability to inhibit the proconvulsant effects of testosterone. The 5α-reduced metabolites of testosterone, DHT and 3α-Diol, had powerful anticonvulsant activity in the PTZ test. Letrozole or finasteride had no effect on seizure protection by DHT and 3α-Diol, but indomethacin partially reversed DHT actions. 3α-Diol but not 3β-Androstanediol, a GABA A receptor-inactive stereoisomer, suppressed 4-aminopyridine-induced spontaneous epileptiform bursting in rat hippocampal slices. Thus, testosterone-derived neurosteroids 3α-Diol and 17β-estradiol could contribute to the net cellular actions of testosterone on neural excitability and seizure susceptibility.
Shuki Mizutani - One of the best experts on this subject based on the ideXlab platform.
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A highly specific heterologous enzyme immunoassay for 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide (Androstanediol-17G) and developmental patterns of urinary Androstanediol-17G excretions.
Steroids, 2020Co-Authors: Toshikazu Onishi, H Takei, Akira Kambegawa, Sumitaka Saisho, Kenichi Kashimada, Satomi Koyama, Shuki MizutaniAbstract:We established a highly specific enzyme immunoassay (EIA) for 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide (Androstanediol-17G). Rabbit antisera raised against 5 alpha-androstane-3 alpha, 11 alpha, 17 beta-triol 17-glucuronide 11-glutaryl bovine serum albumin and a heterologous tracer of Androstanediol-17G conjugated with horseradish peroxidase at the glucuronic acid group were used. The EIA showed excellent specificity: there were no remarkable cross-reactivities with related androgens. The assay range for urine samples was 0.3-30 ng/ml. Recoveries of standards added to samples were 100-108%. Intra-assay and inter-assay coefficients of variation were 2.9-4.4% and 5.7-7.9%, respectively. The EIA was applied to urine samples of 407 males and 322 females to determine developmental patterns and normal ranges of Androstanediol-17G excretions in 11 age groups (0 y, 1 y, 2-3 y, 4-5 y, 6-7 y, 8-9 y, 10-11 y, 12-13 y, 14-15 y, 16-17 y, and over 18 y). Urinary Androstanediol-17G/creatinine (Androstanediol-17G/Cre) ratios in both sexes were high in infancy, tended to decrease during childhood, and began to increase near adolescence. While Androstanediol-17G/Cre ratio in girls increased at 8-9 y and reached a plateau during adolescence, that in boys increased at 10-11 y and continued to increase throughout adolescence. Androstanediol-17G/Cre ratios in girls were higher than those in boys at 6-7 y (P < 0.05) and at 8-9 y (P < 0.01). Androstanediol-17G/Cre ratios in boys were higher than those in girls at 12-13 y and at older ages (P < 0.01). These developmental patterns are parallel to age-related changes in androgenicity and serum Androstanediol-17G, suggesting that urinary Androstanediol-17G/Cre ratio could be a good marker for androgenicity in childhood.
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a highly specific heterologous enzyme immunoassay for 5α androstane 3α 17β diol 17 glucuronide Androstanediol 17g and developmental patterns of urinary Androstanediol 17g excretions
Steroids, 2002Co-Authors: Toshikazu Onishi, H Takei, Akira Kambegawa, Sumitaka Saisho, Kenichi Kashimada, Satomi Koyama, Shuki MizutaniAbstract:We established a highly specific enzyme immunoassay (EIA) for 5α-androstane-3α, 17β-diol 17-glucuronide (Androstanediol-17G). Rabbit antisera raised against 5α-androstane-3α, 11α, 17β-triol 17-glucuronide 11-glutaryl bovine serum albumin and a heterologous tracer of Androstanediol-17G conjugated with horseradish peroxidase at the glucuronic acid group were used. The EIA showed excellent specificity: there were no remarkable cross-reactivities with related androgens. The assay range for urine samples was 0.3–30 ng/ml. Recoveries of standards added to samples were 100–108%. Intra-assay and inter-assay coefficients of variation were 2.9–4.4% and 5.7–7.9%, respectively. The EIA was applied to urine samples of 407 males and 322 females to determine developmental patterns and normal ranges of Androstanediol-17G excretions in 11 age groups (0 y, 1 y, 2–3 y, 4–5 y, 6–7 y, 8–9 y, 10–11 y, 12–13 y, 14–15 y, 16–17 y, and over 18 y). Urinary Androstanediol-17G/creatinine (Androstanediol-17G/Cre) ratios in both sexes were high in infancy, tended to decrease during childhood, and began to increase near adolescence. While Androstanediol-17G/Cre ratio in girls increased at 8–9 y and reached a plateau during adolescence, that in boys increased at 10–11 y and continued to increase throughout adolescence. Androstanediol-17G/Cre ratios in girls were higher than those in boys at 6–7 y (P < 0.05) and at 8–9 y (P < 0.01). Androstanediol-17G/Cre ratios in boys were higher than those in girls at 12–13 y and at older ages (P < 0.01). These developmental patterns are parallel to age-related changes in androgenicity and serum Androstanediol-17G, suggesting that urinary Androstanediol-17G/Cre ratio could be a good marker for androgenicity in childhood.
Kumar Ramu - One of the best experts on this subject based on the ideXlab platform.
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a high performance liquid chromatography tandem mass spectrometry assay of the androgenic neurosteroid 3α Androstanediol 5α androstane 3α 17β diol in plasma
Steroids, 2005Co-Authors: Doodipala Samba Reddy, Lata Venkatarangan, Benjamin Chien, Kumar RamuAbstract:Abstract The testosterone metabolite 3α-Androstanediol (5α-androstane-3α,17-diol) is a potential GABA A receptor-modulating neurosteroid with anticonvulsant properties and hence could act as a key neuromodulator in the central nervous system. However, there is no specific and sensitive assay for quantitative determination of the androgenic neurosteroid 3α-Androstanediol in biological samples. We have established a liquid chromatography–tandem mass spectrometry (LC–MS–MS) assay to measure 3α-Androstanediol in rat plasma. Standard 3α-Androstanediol added to rat plasma has been successfully analysed with excellent linearity, specificity, sensitivity, and reproducibility. The sensitivity of the method was
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A high-performance liquid chromatography–tandem mass spectrometry assay of the androgenic neurosteroid 3α-Androstanediol (5α-androstane-3α,17β-diol) in plasma
Steroids, 2005Co-Authors: Doodipala Samba Reddy, Lata Venkatarangan, Benjamin Chien, Kumar RamuAbstract:Abstract The testosterone metabolite 3α-Androstanediol (5α-androstane-3α,17-diol) is a potential GABA A receptor-modulating neurosteroid with anticonvulsant properties and hence could act as a key neuromodulator in the central nervous system. However, there is no specific and sensitive assay for quantitative determination of the androgenic neurosteroid 3α-Androstanediol in biological samples. We have established a liquid chromatography–tandem mass spectrometry (LC–MS–MS) assay to measure 3α-Androstanediol in rat plasma. Standard 3α-Androstanediol added to rat plasma has been successfully analysed with excellent linearity, specificity, sensitivity, and reproducibility. The sensitivity of the method was
Leslie I Rose - One of the best experts on this subject based on the ideXlab platform.
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Serum Androstanediol glucuronide in women with facial hirsutism.
Journal of the American Academy of Dermatology, 1992Co-Authors: Karl Salman, Richard L Spielvogel, Leon H Shulman, Jeffrey L Miller, Raymond E Vanderlinde, Leslie I RoseAbstract:Measurement of serum 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-diolG) has been proposed as a useful biochemical marker of peripheral androgen metabolism. Is 3 alpha-diol G a useful biochemical marker of peripheral androgen metabolism and does it correlate with degree of facial hirsutism? Our purpose was to assess possible correlation between serum 3 alpha-diol G and degree of facial hirsutism and to compare serum 3 alpha-diol G levels with levels of other commonly measured serum androgens. Twenty-three consecutive women with facial hirsutism were studied, and serum concentrations of 3 alpha-diol G, testosterone (total, free, and biologically active portions), dehydroepiandrosterone sulfate, and androstenedione were measured. There was no correlation between serum 3 alpha-diol G levels and degree of facial hirsutism. There was a correlation between levels of 3 alpha-diol G and dehydroepiandrosterone sulfate (p less than 0.01), biologically active testosterone (p = 0.01), free free testosterone (p less than 0.02), and androstenedione (p less than 0.05). Serum 3 alpha-diol G concentrations have no correlation with degree of facial hirsutism and do not provide additional information over the commonly measured androgens.
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serum Androstanediol glucuronide in women with facial hirsutism
Journal of The American Academy of Dermatology, 1992Co-Authors: Karl Salman, Richard L Spielvogel, Leon H Shulman, Jeffrey L Miller, Raymond E Vanderlinde, Leslie I RoseAbstract:Background: Measurement of serum 5α-androstane-3α,17β-diol glucuronide (3α-diol G) has been proposed as a useful biochemical marker of peripheral androgen metabolism. Is 3α-diol G a useful biochemical marker of peripheral androgen metabolism and does it correlate with degree of facial hirsutism? Objective: Our purpose was to assess possible correlation between serum 3α-diol G and degree of facial hirsutism and to compare serum 3α-diol G levels with levels of other commonly measured serum androgens. Methods: Twenty-three consecutive women with facial hirsutism were studied, and serum concentrations of 3α-diol G, testosterone (total, free, and biologically active portions), dehydroepiandrosterone sulfate, and androstenedione were measured. Results: There was no correlation between serum 3α-diol G levels and degree of facial hirsutism. There was a correlation between levels of 3α-diol G and dehydroepiandrosterone sulfate ( p p = 0.01), free testosterone ( p p Conclusion: Serum 3α-diol G concentrations have no correlation with degree of facial hirsutism and do not provide additional information over the commonly measured androgens.
Toshikazu Onishi - One of the best experts on this subject based on the ideXlab platform.
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A highly specific heterologous enzyme immunoassay for 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide (Androstanediol-17G) and developmental patterns of urinary Androstanediol-17G excretions.
Steroids, 2020Co-Authors: Toshikazu Onishi, H Takei, Akira Kambegawa, Sumitaka Saisho, Kenichi Kashimada, Satomi Koyama, Shuki MizutaniAbstract:We established a highly specific enzyme immunoassay (EIA) for 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide (Androstanediol-17G). Rabbit antisera raised against 5 alpha-androstane-3 alpha, 11 alpha, 17 beta-triol 17-glucuronide 11-glutaryl bovine serum albumin and a heterologous tracer of Androstanediol-17G conjugated with horseradish peroxidase at the glucuronic acid group were used. The EIA showed excellent specificity: there were no remarkable cross-reactivities with related androgens. The assay range for urine samples was 0.3-30 ng/ml. Recoveries of standards added to samples were 100-108%. Intra-assay and inter-assay coefficients of variation were 2.9-4.4% and 5.7-7.9%, respectively. The EIA was applied to urine samples of 407 males and 322 females to determine developmental patterns and normal ranges of Androstanediol-17G excretions in 11 age groups (0 y, 1 y, 2-3 y, 4-5 y, 6-7 y, 8-9 y, 10-11 y, 12-13 y, 14-15 y, 16-17 y, and over 18 y). Urinary Androstanediol-17G/creatinine (Androstanediol-17G/Cre) ratios in both sexes were high in infancy, tended to decrease during childhood, and began to increase near adolescence. While Androstanediol-17G/Cre ratio in girls increased at 8-9 y and reached a plateau during adolescence, that in boys increased at 10-11 y and continued to increase throughout adolescence. Androstanediol-17G/Cre ratios in girls were higher than those in boys at 6-7 y (P < 0.05) and at 8-9 y (P < 0.01). Androstanediol-17G/Cre ratios in boys were higher than those in girls at 12-13 y and at older ages (P < 0.01). These developmental patterns are parallel to age-related changes in androgenicity and serum Androstanediol-17G, suggesting that urinary Androstanediol-17G/Cre ratio could be a good marker for androgenicity in childhood.
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a highly specific heterologous enzyme immunoassay for 5α androstane 3α 17β diol 17 glucuronide Androstanediol 17g and developmental patterns of urinary Androstanediol 17g excretions
Steroids, 2002Co-Authors: Toshikazu Onishi, H Takei, Akira Kambegawa, Sumitaka Saisho, Kenichi Kashimada, Satomi Koyama, Shuki MizutaniAbstract:We established a highly specific enzyme immunoassay (EIA) for 5α-androstane-3α, 17β-diol 17-glucuronide (Androstanediol-17G). Rabbit antisera raised against 5α-androstane-3α, 11α, 17β-triol 17-glucuronide 11-glutaryl bovine serum albumin and a heterologous tracer of Androstanediol-17G conjugated with horseradish peroxidase at the glucuronic acid group were used. The EIA showed excellent specificity: there were no remarkable cross-reactivities with related androgens. The assay range for urine samples was 0.3–30 ng/ml. Recoveries of standards added to samples were 100–108%. Intra-assay and inter-assay coefficients of variation were 2.9–4.4% and 5.7–7.9%, respectively. The EIA was applied to urine samples of 407 males and 322 females to determine developmental patterns and normal ranges of Androstanediol-17G excretions in 11 age groups (0 y, 1 y, 2–3 y, 4–5 y, 6–7 y, 8–9 y, 10–11 y, 12–13 y, 14–15 y, 16–17 y, and over 18 y). Urinary Androstanediol-17G/creatinine (Androstanediol-17G/Cre) ratios in both sexes were high in infancy, tended to decrease during childhood, and began to increase near adolescence. While Androstanediol-17G/Cre ratio in girls increased at 8–9 y and reached a plateau during adolescence, that in boys increased at 10–11 y and continued to increase throughout adolescence. Androstanediol-17G/Cre ratios in girls were higher than those in boys at 6–7 y (P < 0.05) and at 8–9 y (P < 0.01). Androstanediol-17G/Cre ratios in boys were higher than those in girls at 12–13 y and at older ages (P < 0.01). These developmental patterns are parallel to age-related changes in androgenicity and serum Androstanediol-17G, suggesting that urinary Androstanediol-17G/Cre ratio could be a good marker for androgenicity in childhood.
