The Experts below are selected from a list of 4341 Experts worldwide ranked by ideXlab platform
J. Arunakaran - One of the best experts on this subject based on the ideXlab platform.
-
effects of vitamins c and e on Steroidogenic Enzymes mrna expression in polychlorinated biphenyl aroclor 1254 exposed adult rat leydig cells
Toxicology, 2007Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions including gonadal functions in humans and mammals. The present study was conducted to elucidate the protective role of vitamins C and E against Aroclor 1254-induced changes in Leydig cell Steroidogenic acute regulatory (StAR) protein and Steroidogenic Enzymes mRNA expression. Adult male rats were dosed for 30 days with daily intraperitoneal (i.p.) injection of 2 mg/kg Aroclor 1254 or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw day) while the other group was treated with vitamin E (50 mg/kg bw day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol. The serum androgen binding protein was also estimated. Testes were quickly removed and Leydig cells were isolated in aseptic condition. Purity of Leydig cells was determined by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining methods. Purified Leydig cells were used for quantification of androgen and estrogen receptors. In addition, total RNA was isolated from control and treated Leydig cells to monitor the steady-state mRNA levels by RT-PCR for StAR protein, cytochrome P(450)scc, 3beta-HSD and 17beta-HSD. Aroclor 1254 treatment significantly reduced the serum LH, FSH, testosterone, estradiol and androgen binding protein. In addition to this, Leydig cell androgen and estrogen receptors were markedly decreased. RT-PCR analysis of StAR mRNA level did not alter Aroclor 1254 treatment while Steroidogenic Enzymes such as cytochrome P(450)scc, 3beta-HSD and 17beta-HSD mRNAs were drastically decreased in Aroclor 1254 treatment. However, the simultaneous administration of vitamins C or E in Aroclor 1254-exposed rats resulted a significant restoration of all the above-mentioned parameters to the control level. These observations suggest that vitamins C and E have ameliorative role against PCBs-induced testicular Leydig cells dysfunction.
-
effects of vitamins c and e on Steroidogenic Enzymes mrna expression in polychlorinated biphenyl aroclor 1254 exposed adult rat leydig cells
Toxicology, 2007Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Abstract Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions including gonadal functions in humans and mammals. The present study was conducted to elucidate the protective role of vitamins C and E against Aroclor 1254-induced changes in Leydig cell Steroidogenic acute regulatory (StAR) protein and Steroidogenic Enzymes mRNA expression. Adult male rats were dosed for 30 days with daily intraperitoneal (i.p.) injection of 2 mg/kg Aroclor 1254 or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw day) while the other group was treated with vitamin E (50 mg/kg bw day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol. The serum androgen binding protein was also estimated. Testes were quickly removed and Leydig cells were isolated in aseptic condition. Purity of Leydig cells was determined by 3β-hydroxysteroid dehydrogenase (3β-HSD) staining methods. Purified Leydig cells were used for quantification of androgen and estrogen receptors. In addition, total RNA was isolated from control and treated Leydig cells to monitor the steady-state mRNA levels by RT-PCR for StAR protein, cytochrome P 450 scc, 3β-HSD and 17β-HSD. Aroclor 1254 treatment significantly reduced the serum LH, FSH, testosterone, estradiol and androgen binding protein. In addition to this, Leydig cell androgen and estrogen receptors were markedly decreased. RT-PCR analysis of StAR mRNA level did not alter Aroclor 1254 treatment while Steroidogenic Enzymes such as cytochrome P 450 scc, 3β-HSD and 17β-HSD mRNAs were drastically decreased in Aroclor 1254 treatment. However, the simultaneous administration of vitamins C or E in Aroclor 1254-exposed rats resulted a significant restoration of all the above-mentioned parameters to the control level. These observations suggest that vitamins C and E have ameliorative role against PCBs-induced testicular Leydig cells dysfunction.
-
the inhibitory effects of polychlorinated biphenyl aroclor 1254 on leydig cell lh receptors Steroidogenic Enzymes and antioxidant Enzymes in adult rats
Reproductive Toxicology, 2005Co-Authors: Palaniappan Murugesan, P. Kanagaraj, K Balasubramanian, M M Aruldhas, Sambandam Yuvaraj, J. ArunakaranAbstract:AbstractPolychlorinated biphenyls (PCBs) are global pollutants of major concern to human and animal reproductive health. The present study hasexamined the impact of Aroclor 1254 exposure on oxidative stress and testicular Leydig cell function. Adult albino male rats of the Wistarstrain were dosed for 30 days with daily intraperitoneal injections of 2mg/kg Aroclor 1254 or vehicle (corn oil). One day after the lasttreatment, animals were euthanized and blood collected for the assay of serum testosterone and estradiol. Testes were removed and Leydigcells were isolated for the assay of luteinizing hormone (LH) receptors, Steroidogenic Enzymes cytochrome P450 side chain cleavage enzyme(P450 scc), 3 -hydroxysteroid dehydrogenase (3 -HSD) and 17 -hydroxysteroid dehydrogenase (17 -HSD). Cellular antioxidant Enzymessuperoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-S -transferase (GST)were also assayed. Lipid peroxidation (LPO) and reactive oxygen species (ROS) were quantified. Results showed that Aroclor 1254 exposurelowered serum testosterone and estradiol levels. Leydig cell LH receptor density, activities of the Steroidogenic Enzymes P450 scc, 3 -HSD,17 -HSD, antioxidant Enzymes SOD, CAT, GPX, GR, and GST were significantly diminished whereas, LPO and ROS significantly elevated.Taken together, these results suggest that inefficient LH receptors, Steroidogenic Enzymes and antioxidant Enzymes are possible mechanismsby which Aroclor 1254 treatment disrupts Leydig cell steroidogenesis.© 2004 Elsevier Inc. All rights reserved.
Palaniappan Murugesan - One of the best experts on this subject based on the ideXlab platform.
-
effects of vitamins c and e on Steroidogenic Enzymes mrna expression in polychlorinated biphenyl aroclor 1254 exposed adult rat leydig cells
Toxicology, 2007Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions including gonadal functions in humans and mammals. The present study was conducted to elucidate the protective role of vitamins C and E against Aroclor 1254-induced changes in Leydig cell Steroidogenic acute regulatory (StAR) protein and Steroidogenic Enzymes mRNA expression. Adult male rats were dosed for 30 days with daily intraperitoneal (i.p.) injection of 2 mg/kg Aroclor 1254 or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw day) while the other group was treated with vitamin E (50 mg/kg bw day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol. The serum androgen binding protein was also estimated. Testes were quickly removed and Leydig cells were isolated in aseptic condition. Purity of Leydig cells was determined by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining methods. Purified Leydig cells were used for quantification of androgen and estrogen receptors. In addition, total RNA was isolated from control and treated Leydig cells to monitor the steady-state mRNA levels by RT-PCR for StAR protein, cytochrome P(450)scc, 3beta-HSD and 17beta-HSD. Aroclor 1254 treatment significantly reduced the serum LH, FSH, testosterone, estradiol and androgen binding protein. In addition to this, Leydig cell androgen and estrogen receptors were markedly decreased. RT-PCR analysis of StAR mRNA level did not alter Aroclor 1254 treatment while Steroidogenic Enzymes such as cytochrome P(450)scc, 3beta-HSD and 17beta-HSD mRNAs were drastically decreased in Aroclor 1254 treatment. However, the simultaneous administration of vitamins C or E in Aroclor 1254-exposed rats resulted a significant restoration of all the above-mentioned parameters to the control level. These observations suggest that vitamins C and E have ameliorative role against PCBs-induced testicular Leydig cells dysfunction.
-
effects of vitamins c and e on Steroidogenic Enzymes mrna expression in polychlorinated biphenyl aroclor 1254 exposed adult rat leydig cells
Toxicology, 2007Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Abstract Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions including gonadal functions in humans and mammals. The present study was conducted to elucidate the protective role of vitamins C and E against Aroclor 1254-induced changes in Leydig cell Steroidogenic acute regulatory (StAR) protein and Steroidogenic Enzymes mRNA expression. Adult male rats were dosed for 30 days with daily intraperitoneal (i.p.) injection of 2 mg/kg Aroclor 1254 or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw day) while the other group was treated with vitamin E (50 mg/kg bw day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol. The serum androgen binding protein was also estimated. Testes were quickly removed and Leydig cells were isolated in aseptic condition. Purity of Leydig cells was determined by 3β-hydroxysteroid dehydrogenase (3β-HSD) staining methods. Purified Leydig cells were used for quantification of androgen and estrogen receptors. In addition, total RNA was isolated from control and treated Leydig cells to monitor the steady-state mRNA levels by RT-PCR for StAR protein, cytochrome P 450 scc, 3β-HSD and 17β-HSD. Aroclor 1254 treatment significantly reduced the serum LH, FSH, testosterone, estradiol and androgen binding protein. In addition to this, Leydig cell androgen and estrogen receptors were markedly decreased. RT-PCR analysis of StAR mRNA level did not alter Aroclor 1254 treatment while Steroidogenic Enzymes such as cytochrome P 450 scc, 3β-HSD and 17β-HSD mRNAs were drastically decreased in Aroclor 1254 treatment. However, the simultaneous administration of vitamins C or E in Aroclor 1254-exposed rats resulted a significant restoration of all the above-mentioned parameters to the control level. These observations suggest that vitamins C and E have ameliorative role against PCBs-induced testicular Leydig cells dysfunction.
-
the inhibitory effects of polychlorinated biphenyl aroclor 1254 on leydig cell lh receptors Steroidogenic Enzymes and antioxidant Enzymes in adult rats
Reproductive Toxicology, 2005Co-Authors: Palaniappan Murugesan, P. Kanagaraj, K Balasubramanian, M M Aruldhas, Sambandam Yuvaraj, J. ArunakaranAbstract:AbstractPolychlorinated biphenyls (PCBs) are global pollutants of major concern to human and animal reproductive health. The present study hasexamined the impact of Aroclor 1254 exposure on oxidative stress and testicular Leydig cell function. Adult albino male rats of the Wistarstrain were dosed for 30 days with daily intraperitoneal injections of 2mg/kg Aroclor 1254 or vehicle (corn oil). One day after the lasttreatment, animals were euthanized and blood collected for the assay of serum testosterone and estradiol. Testes were removed and Leydigcells were isolated for the assay of luteinizing hormone (LH) receptors, Steroidogenic Enzymes cytochrome P450 side chain cleavage enzyme(P450 scc), 3 -hydroxysteroid dehydrogenase (3 -HSD) and 17 -hydroxysteroid dehydrogenase (17 -HSD). Cellular antioxidant Enzymessuperoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-S -transferase (GST)were also assayed. Lipid peroxidation (LPO) and reactive oxygen species (ROS) were quantified. Results showed that Aroclor 1254 exposurelowered serum testosterone and estradiol levels. Leydig cell LH receptor density, activities of the Steroidogenic Enzymes P450 scc, 3 -HSD,17 -HSD, antioxidant Enzymes SOD, CAT, GPX, GR, and GST were significantly diminished whereas, LPO and ROS significantly elevated.Taken together, these results suggest that inefficient LH receptors, Steroidogenic Enzymes and antioxidant Enzymes are possible mechanismsby which Aroclor 1254 treatment disrupts Leydig cell steroidogenesis.© 2004 Elsevier Inc. All rights reserved.
Kjell Wikvall - One of the best experts on this subject based on the ideXlab platform.
-
1α 25 dihydroxyvitamin d3 affects hormone production and expression of Steroidogenic Enzymes in human adrenocortical nci h295r cells
Biochimica et Biophysica Acta, 2010Co-Authors: Johan Lundqvist, Maria Norlin, Kjell WikvallAbstract:The current study presents data indicating that 1alpha,25-dihydroxyvitamin D(3) affects the production of hormones and expression of crucial Steroidogenic Enzymes in the human adrenocortical cell line NCI-H295R. This cell line is widely used as a model for adrenal steroidogenesis. Treatment of the cells with 1alpha,25-dihydroxyvitamin D(3) suppressed the levels of corticosterone, aldosterone, DHEA, DHEA-sulfate and androstenedione in the culture medium. In order to study the mechanisms behind this suppression of hormone production, we investigated the effects of 1alpha,25-dihydroxyvitamin D(3) on important genes and Enzymes controlling the biosynthesis of adrenal hormones. The mRNA levels were decreased for CYP21A2 while they were increased for CYP11A1 and CYP17A1. No significant changes were observed in mRNA for CYP11B1, CYP11B2 or 3beta-hydroxysteroid dehydrogenase (3betaHSD). In similarity with the effects on mRNA levels, also the endogenous enzyme activity of CYP21A2 decreased after treatment with 1alpha,25-dihydroxyvitamin D(3). Interestingly, the two CYP17A1-mediated activities were influenced reciprocally - the 17alpha-hydroxylase activity increased whereas the 17,20-lyase activity decreased. The current data indicate that the 1alpha,25-dihydroxyvitamin D(3)-mediated decrease in corticosterone and androgen production is due to suppression of the 21-hydroxylase activity by CYP21A2 and the 17,20-lyase activity by CYP17A1, respectively. In conclusion, the current study reports novel findings on 1alpha,25-dihydroxyvitamin D(3)-mediated effects on hormone production and regulation of genes and Enzymes involved in steroidogenesis in the adrenocortical NCI-H295R cell line, a model for human adrenal cortex.
-
1α 25 dihydroxyvitamin d3 affects hormone production and expression of Steroidogenic Enzymes in human adrenocortical nci h295r cells
Biochimica et Biophysica Acta, 2010Co-Authors: Johan Lundqvist, Maria Norlin, Kjell WikvallAbstract:Abstract The current study presents data indicating that 1α,25-dihydroxyvitamin D3 affects the production of hormones and expression of crucial Steroidogenic Enzymes in the human adrenocortical cell line NCI-H295R. This cell line is widely used as a model for adrenal steroidogenesis. Treatment of the cells with 1α,25-dihydroxyvitamin D3 suppressed the levels of corticosterone, aldosterone, DHEA, DHEA-sulfate and androstenedione in the culture medium. In order to study the mechanisms behind this suppression of hormone production, we investigated the effects of 1α,25-dihydroxyvitamin D3 on important genes and Enzymes controlling the biosynthesis of adrenal hormones. The mRNA levels were decreased for CYP21A2 while they were increased for CYP11A1 and CYP17A1. No significant changes were observed in mRNA for CYP11B1, CYP11B2 or 3β-hydroxysteroid dehydrogenase (3βHSD). In similarity with the effects on mRNA levels, also the endogenous enzyme activity of CYP21A2 decreased after treatment with 1α,25-dihydroxyvitamin D3. Interestingly, the two CYP17A1-mediated activities were influenced reciprocally — the 17α-hydroxylase activity increased whereas the 17,20-lyase activity decreased. The current data indicate that the 1α,25-dihydroxyvitamin D3-mediated decrease in corticosterone and androgen production is due to suppression of the 21-hydroxylase activity by CYP21A2 and the 17,20-lyase activity by CYP17A1, respectively. In conclusion, the current study reports novel findings on 1α,25-dihydroxyvitamin D3-mediated effects on hormone production and regulation of genes and Enzymes involved in steroidogenesis in the adrenocortical NCI-H295R cell line, a model for human adrenal cortex.
K Balasubramanian - One of the best experts on this subject based on the ideXlab platform.
-
effects of vitamins c and e on Steroidogenic Enzymes mrna expression in polychlorinated biphenyl aroclor 1254 exposed adult rat leydig cells
Toxicology, 2007Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions including gonadal functions in humans and mammals. The present study was conducted to elucidate the protective role of vitamins C and E against Aroclor 1254-induced changes in Leydig cell Steroidogenic acute regulatory (StAR) protein and Steroidogenic Enzymes mRNA expression. Adult male rats were dosed for 30 days with daily intraperitoneal (i.p.) injection of 2 mg/kg Aroclor 1254 or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw day) while the other group was treated with vitamin E (50 mg/kg bw day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol. The serum androgen binding protein was also estimated. Testes were quickly removed and Leydig cells were isolated in aseptic condition. Purity of Leydig cells was determined by 3beta-hydroxysteroid dehydrogenase (3beta-HSD) staining methods. Purified Leydig cells were used for quantification of androgen and estrogen receptors. In addition, total RNA was isolated from control and treated Leydig cells to monitor the steady-state mRNA levels by RT-PCR for StAR protein, cytochrome P(450)scc, 3beta-HSD and 17beta-HSD. Aroclor 1254 treatment significantly reduced the serum LH, FSH, testosterone, estradiol and androgen binding protein. In addition to this, Leydig cell androgen and estrogen receptors were markedly decreased. RT-PCR analysis of StAR mRNA level did not alter Aroclor 1254 treatment while Steroidogenic Enzymes such as cytochrome P(450)scc, 3beta-HSD and 17beta-HSD mRNAs were drastically decreased in Aroclor 1254 treatment. However, the simultaneous administration of vitamins C or E in Aroclor 1254-exposed rats resulted a significant restoration of all the above-mentioned parameters to the control level. These observations suggest that vitamins C and E have ameliorative role against PCBs-induced testicular Leydig cells dysfunction.
-
effects of vitamins c and e on Steroidogenic Enzymes mrna expression in polychlorinated biphenyl aroclor 1254 exposed adult rat leydig cells
Toxicology, 2007Co-Authors: Palaniappan Murugesan, K Balasubramanian, Thirupathi Muthusamy, J. ArunakaranAbstract:Abstract Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions including gonadal functions in humans and mammals. The present study was conducted to elucidate the protective role of vitamins C and E against Aroclor 1254-induced changes in Leydig cell Steroidogenic acute regulatory (StAR) protein and Steroidogenic Enzymes mRNA expression. Adult male rats were dosed for 30 days with daily intraperitoneal (i.p.) injection of 2 mg/kg Aroclor 1254 or vehicle (corn oil). One group of rats was treated with vitamin C (100 mg/kg bw day) while the other group was treated with vitamin E (50 mg/kg bw day) orally, simultaneously with Aroclor 1254 for 30 days. One day after the last treatment, animals were euthanized and blood was collected for the assay of serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol. The serum androgen binding protein was also estimated. Testes were quickly removed and Leydig cells were isolated in aseptic condition. Purity of Leydig cells was determined by 3β-hydroxysteroid dehydrogenase (3β-HSD) staining methods. Purified Leydig cells were used for quantification of androgen and estrogen receptors. In addition, total RNA was isolated from control and treated Leydig cells to monitor the steady-state mRNA levels by RT-PCR for StAR protein, cytochrome P 450 scc, 3β-HSD and 17β-HSD. Aroclor 1254 treatment significantly reduced the serum LH, FSH, testosterone, estradiol and androgen binding protein. In addition to this, Leydig cell androgen and estrogen receptors were markedly decreased. RT-PCR analysis of StAR mRNA level did not alter Aroclor 1254 treatment while Steroidogenic Enzymes such as cytochrome P 450 scc, 3β-HSD and 17β-HSD mRNAs were drastically decreased in Aroclor 1254 treatment. However, the simultaneous administration of vitamins C or E in Aroclor 1254-exposed rats resulted a significant restoration of all the above-mentioned parameters to the control level. These observations suggest that vitamins C and E have ameliorative role against PCBs-induced testicular Leydig cells dysfunction.
-
the inhibitory effects of polychlorinated biphenyl aroclor 1254 on leydig cell lh receptors Steroidogenic Enzymes and antioxidant Enzymes in adult rats
Reproductive Toxicology, 2005Co-Authors: Palaniappan Murugesan, P. Kanagaraj, K Balasubramanian, M M Aruldhas, Sambandam Yuvaraj, J. ArunakaranAbstract:AbstractPolychlorinated biphenyls (PCBs) are global pollutants of major concern to human and animal reproductive health. The present study hasexamined the impact of Aroclor 1254 exposure on oxidative stress and testicular Leydig cell function. Adult albino male rats of the Wistarstrain were dosed for 30 days with daily intraperitoneal injections of 2mg/kg Aroclor 1254 or vehicle (corn oil). One day after the lasttreatment, animals were euthanized and blood collected for the assay of serum testosterone and estradiol. Testes were removed and Leydigcells were isolated for the assay of luteinizing hormone (LH) receptors, Steroidogenic Enzymes cytochrome P450 side chain cleavage enzyme(P450 scc), 3 -hydroxysteroid dehydrogenase (3 -HSD) and 17 -hydroxysteroid dehydrogenase (17 -HSD). Cellular antioxidant Enzymessuperoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-S -transferase (GST)were also assayed. Lipid peroxidation (LPO) and reactive oxygen species (ROS) were quantified. Results showed that Aroclor 1254 exposurelowered serum testosterone and estradiol levels. Leydig cell LH receptor density, activities of the Steroidogenic Enzymes P450 scc, 3 -HSD,17 -HSD, antioxidant Enzymes SOD, CAT, GPX, GR, and GST were significantly diminished whereas, LPO and ROS significantly elevated.Taken together, these results suggest that inefficient LH receptors, Steroidogenic Enzymes and antioxidant Enzymes are possible mechanismsby which Aroclor 1254 treatment disrupts Leydig cell steroidogenesis.© 2004 Elsevier Inc. All rights reserved.
Johan Lundqvist - One of the best experts on this subject based on the ideXlab platform.
-
1α 25 dihydroxyvitamin d3 affects hormone production and expression of Steroidogenic Enzymes in human adrenocortical nci h295r cells
Biochimica et Biophysica Acta, 2010Co-Authors: Johan Lundqvist, Maria Norlin, Kjell WikvallAbstract:The current study presents data indicating that 1alpha,25-dihydroxyvitamin D(3) affects the production of hormones and expression of crucial Steroidogenic Enzymes in the human adrenocortical cell line NCI-H295R. This cell line is widely used as a model for adrenal steroidogenesis. Treatment of the cells with 1alpha,25-dihydroxyvitamin D(3) suppressed the levels of corticosterone, aldosterone, DHEA, DHEA-sulfate and androstenedione in the culture medium. In order to study the mechanisms behind this suppression of hormone production, we investigated the effects of 1alpha,25-dihydroxyvitamin D(3) on important genes and Enzymes controlling the biosynthesis of adrenal hormones. The mRNA levels were decreased for CYP21A2 while they were increased for CYP11A1 and CYP17A1. No significant changes were observed in mRNA for CYP11B1, CYP11B2 or 3beta-hydroxysteroid dehydrogenase (3betaHSD). In similarity with the effects on mRNA levels, also the endogenous enzyme activity of CYP21A2 decreased after treatment with 1alpha,25-dihydroxyvitamin D(3). Interestingly, the two CYP17A1-mediated activities were influenced reciprocally - the 17alpha-hydroxylase activity increased whereas the 17,20-lyase activity decreased. The current data indicate that the 1alpha,25-dihydroxyvitamin D(3)-mediated decrease in corticosterone and androgen production is due to suppression of the 21-hydroxylase activity by CYP21A2 and the 17,20-lyase activity by CYP17A1, respectively. In conclusion, the current study reports novel findings on 1alpha,25-dihydroxyvitamin D(3)-mediated effects on hormone production and regulation of genes and Enzymes involved in steroidogenesis in the adrenocortical NCI-H295R cell line, a model for human adrenal cortex.
-
1α 25 dihydroxyvitamin d3 affects hormone production and expression of Steroidogenic Enzymes in human adrenocortical nci h295r cells
Biochimica et Biophysica Acta, 2010Co-Authors: Johan Lundqvist, Maria Norlin, Kjell WikvallAbstract:Abstract The current study presents data indicating that 1α,25-dihydroxyvitamin D3 affects the production of hormones and expression of crucial Steroidogenic Enzymes in the human adrenocortical cell line NCI-H295R. This cell line is widely used as a model for adrenal steroidogenesis. Treatment of the cells with 1α,25-dihydroxyvitamin D3 suppressed the levels of corticosterone, aldosterone, DHEA, DHEA-sulfate and androstenedione in the culture medium. In order to study the mechanisms behind this suppression of hormone production, we investigated the effects of 1α,25-dihydroxyvitamin D3 on important genes and Enzymes controlling the biosynthesis of adrenal hormones. The mRNA levels were decreased for CYP21A2 while they were increased for CYP11A1 and CYP17A1. No significant changes were observed in mRNA for CYP11B1, CYP11B2 or 3β-hydroxysteroid dehydrogenase (3βHSD). In similarity with the effects on mRNA levels, also the endogenous enzyme activity of CYP21A2 decreased after treatment with 1α,25-dihydroxyvitamin D3. Interestingly, the two CYP17A1-mediated activities were influenced reciprocally — the 17α-hydroxylase activity increased whereas the 17,20-lyase activity decreased. The current data indicate that the 1α,25-dihydroxyvitamin D3-mediated decrease in corticosterone and androgen production is due to suppression of the 21-hydroxylase activity by CYP21A2 and the 17,20-lyase activity by CYP17A1, respectively. In conclusion, the current study reports novel findings on 1α,25-dihydroxyvitamin D3-mediated effects on hormone production and regulation of genes and Enzymes involved in steroidogenesis in the adrenocortical NCI-H295R cell line, a model for human adrenal cortex.
