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Androstanediol

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Doodipala Samba Reddy – 1st expert on this subject based on the ideXlab platform

  • the testosterone derived neurosteroid Androstanediol is a positive allosteric modulator of gabaa receptors
    Journal of Pharmacology and Experimental Therapeutics, 2010
    Co-Authors: Doodipala Samba Reddy, Kuihuan Jian

    Abstract:

    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.

  • a high performance liquid chromatography tandem mass spectrometry assay of the androgenic neurosteroid 3α Androstanediol 5α androstane 3α 17β diol in plasma
    Steroids, 2005
    Co-Authors: Doodipala Samba Reddy, Lata Venkatarangan, Benjamin Chien, Kumar Ramu

    Abstract:

    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

  • A high-performance liquid chromatography–tandem mass spectrometry assay of the androgenic neurosteroid 3α-Androstanediol (5α-androstane-3α,17β-diol) in plasma
    Steroids, 2005
    Co-Authors: Doodipala Samba Reddy, Lata Venkatarangan, Benjamin Chien, Kumar Ramu

    Abstract:

    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

Shuki Mizutani – 2nd expert on this subject based on the ideXlab platform

  • 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, 2020
    Co-Authors: Toshikazu Onishi, H Takei, Akira Kambegawa, Sumitaka Saisho, Kenichi Kashimada, Satomi Koyama, Shuki Mizutani

    Abstract:

    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.

  • 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, 2002
    Co-Authors: Toshikazu Onishi, H Takei, Akira Kambegawa, Sumitaka Saisho, Kenichi Kashimada, Satomi Koyama, Shuki Mizutani

    Abstract:

    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 – 3rd expert on this subject based on the ideXlab platform

  • a high performance liquid chromatography tandem mass spectrometry assay of the androgenic neurosteroid 3α Androstanediol 5α androstane 3α 17β diol in plasma
    Steroids, 2005
    Co-Authors: Doodipala Samba Reddy, Lata Venkatarangan, Benjamin Chien, Kumar Ramu

    Abstract:

    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

  • A high-performance liquid chromatography–tandem mass spectrometry assay of the androgenic neurosteroid 3α-Androstanediol (5α-androstane-3α,17β-diol) in plasma
    Steroids, 2005
    Co-Authors: Doodipala Samba Reddy, Lata Venkatarangan, Benjamin Chien, Kumar Ramu

    Abstract:

    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