Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis
In Wistar rats, hexachlorobenzene (HCB) depresses the gluconeogenic enzyme phosphoenolpyruvate-carboxykinase (PEPCK). In the liver, glucocorticoids (GC) normally regulate the glucose synthesis by acting on PEPCK. Thus, the aim of this work was to investigate, in a time-course study, the effects of H...
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2007
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paper:paper_00062952_v73_n6_p873_Lelli2023-06-08T14:30:35Z Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis Lelli de Angeletti, Sandra Marcela Ceballos, Nora Raquel Mazzetti, Marta Blanca San Martín de Viale, Leonor Carmen Corticosterone Glucocorticoids receptor Gluconeogenesis Hexachlorobenzene Phosphoenol-pyruvate carboxykinase Porphyria allylisopropylacetamide corticosterone corticotropin glucocorticoid receptor glucose griseofulvin hexachlorobenzene phosphoenolpyruvate carboxykinase (GTP) reduced nicotinamide adenine dinucleotide steroid hormone adrenal gland animal experiment article binding affinity biosynthesis controlled study corticosterone blood level female gluconeogenesis intoxication nonhuman pest control porphyria priority journal radioimmunoassay rat receptor binding urine level xenobiotic metabolism Adrenal Glands Animals Corticosterone Endocrine Disruptors Female Gluconeogenesis Hexachlorobenzene Liver Phosphoenolpyruvate Carboxykinase (ATP) Porphyrins Rats Rats, Wistar Receptors, Glucocorticoid In Wistar rats, hexachlorobenzene (HCB) depresses the gluconeogenic enzyme phosphoenolpyruvate-carboxykinase (PEPCK). In the liver, glucocorticoids (GC) normally regulate the glucose synthesis by acting on PEPCK. Thus, the aim of this work was to investigate, in a time-course study, the effects of HCB on plasma GC, its adrenal synthesis and stimulation, and the kinetic parameters of its hepatic receptors (GR) in relation to the gluconeogenic blockage produced by HCB. Plasma corticosterone (CORT) concentration, urinary porphyrins and hepatic PEPCK were determined after 2, 4, 6 and 8 weeks of HCB-treatment. The effect of HCB on kinetic parameters of GR was studied in adrenalectomized porphyric rats after 2, 4 and 8 weeks of treatment. Additionally, adrenal CORT synthesis in the same weeks was measured with or without ACTH. Results show that plasma CORT in intoxicated animals dropped significantly after 2 and 4 weeks of treatment (23% and 58%, respectively), and then remained constant until the 8th week. HCB also promoted a reduction in the number of hepatic GR (50-55%) without modifying affinity. After 8 weeks, when porphyria was well established (40-50-fold increase in urinary porphyrins), a reduction (52%) in hepatic GR number, as well as a decrease in PEPCK activity (56%) were observed. Moreover, CORT biosynthesis in adrenals from intoxicated animals significantly decreased (60%) without changes in ACTH effect. Briefly, this paper shows that HCB causes a disruption in GC and GR. This disturbance could contribute to the negative effect on glucose synthesis through PEPCK regulation, thus modulating porphyria. These results enhance the knowledge about the hormonal disruption produced by chlorinated xenobiotics. © 2006 Elsevier Inc. All rights reserved. Fil:Lelli, S.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ceballos, N.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Mazzetti, M.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:San Martín de Viale, L.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2007 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v73_n6_p873_Lelli http://hdl.handle.net/20.500.12110/paper_00062952_v73_n6_p873_Lelli |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Corticosterone Glucocorticoids receptor Gluconeogenesis Hexachlorobenzene Phosphoenol-pyruvate carboxykinase Porphyria allylisopropylacetamide corticosterone corticotropin glucocorticoid receptor glucose griseofulvin hexachlorobenzene phosphoenolpyruvate carboxykinase (GTP) reduced nicotinamide adenine dinucleotide steroid hormone adrenal gland animal experiment article binding affinity biosynthesis controlled study corticosterone blood level female gluconeogenesis intoxication nonhuman pest control porphyria priority journal radioimmunoassay rat receptor binding urine level xenobiotic metabolism Adrenal Glands Animals Corticosterone Endocrine Disruptors Female Gluconeogenesis Hexachlorobenzene Liver Phosphoenolpyruvate Carboxykinase (ATP) Porphyrins Rats Rats, Wistar Receptors, Glucocorticoid |
| spellingShingle |
Corticosterone Glucocorticoids receptor Gluconeogenesis Hexachlorobenzene Phosphoenol-pyruvate carboxykinase Porphyria allylisopropylacetamide corticosterone corticotropin glucocorticoid receptor glucose griseofulvin hexachlorobenzene phosphoenolpyruvate carboxykinase (GTP) reduced nicotinamide adenine dinucleotide steroid hormone adrenal gland animal experiment article binding affinity biosynthesis controlled study corticosterone blood level female gluconeogenesis intoxication nonhuman pest control porphyria priority journal radioimmunoassay rat receptor binding urine level xenobiotic metabolism Adrenal Glands Animals Corticosterone Endocrine Disruptors Female Gluconeogenesis Hexachlorobenzene Liver Phosphoenolpyruvate Carboxykinase (ATP) Porphyrins Rats Rats, Wistar Receptors, Glucocorticoid Lelli de Angeletti, Sandra Marcela Ceballos, Nora Raquel Mazzetti, Marta Blanca San Martín de Viale, Leonor Carmen Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis |
| topic_facet |
Corticosterone Glucocorticoids receptor Gluconeogenesis Hexachlorobenzene Phosphoenol-pyruvate carboxykinase Porphyria allylisopropylacetamide corticosterone corticotropin glucocorticoid receptor glucose griseofulvin hexachlorobenzene phosphoenolpyruvate carboxykinase (GTP) reduced nicotinamide adenine dinucleotide steroid hormone adrenal gland animal experiment article binding affinity biosynthesis controlled study corticosterone blood level female gluconeogenesis intoxication nonhuman pest control porphyria priority journal radioimmunoassay rat receptor binding urine level xenobiotic metabolism Adrenal Glands Animals Corticosterone Endocrine Disruptors Female Gluconeogenesis Hexachlorobenzene Liver Phosphoenolpyruvate Carboxykinase (ATP) Porphyrins Rats Rats, Wistar Receptors, Glucocorticoid |
| description |
In Wistar rats, hexachlorobenzene (HCB) depresses the gluconeogenic enzyme phosphoenolpyruvate-carboxykinase (PEPCK). In the liver, glucocorticoids (GC) normally regulate the glucose synthesis by acting on PEPCK. Thus, the aim of this work was to investigate, in a time-course study, the effects of HCB on plasma GC, its adrenal synthesis and stimulation, and the kinetic parameters of its hepatic receptors (GR) in relation to the gluconeogenic blockage produced by HCB. Plasma corticosterone (CORT) concentration, urinary porphyrins and hepatic PEPCK were determined after 2, 4, 6 and 8 weeks of HCB-treatment. The effect of HCB on kinetic parameters of GR was studied in adrenalectomized porphyric rats after 2, 4 and 8 weeks of treatment. Additionally, adrenal CORT synthesis in the same weeks was measured with or without ACTH. Results show that plasma CORT in intoxicated animals dropped significantly after 2 and 4 weeks of treatment (23% and 58%, respectively), and then remained constant until the 8th week. HCB also promoted a reduction in the number of hepatic GR (50-55%) without modifying affinity. After 8 weeks, when porphyria was well established (40-50-fold increase in urinary porphyrins), a reduction (52%) in hepatic GR number, as well as a decrease in PEPCK activity (56%) were observed. Moreover, CORT biosynthesis in adrenals from intoxicated animals significantly decreased (60%) without changes in ACTH effect. Briefly, this paper shows that HCB causes a disruption in GC and GR. This disturbance could contribute to the negative effect on glucose synthesis through PEPCK regulation, thus modulating porphyria. These results enhance the knowledge about the hormonal disruption produced by chlorinated xenobiotics. © 2006 Elsevier Inc. All rights reserved. |
| author |
Lelli de Angeletti, Sandra Marcela Ceballos, Nora Raquel Mazzetti, Marta Blanca San Martín de Viale, Leonor Carmen |
| author_facet |
Lelli de Angeletti, Sandra Marcela Ceballos, Nora Raquel Mazzetti, Marta Blanca San Martín de Viale, Leonor Carmen |
| author_sort |
Lelli de Angeletti, Sandra Marcela |
| title |
Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis |
| title_short |
Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis |
| title_full |
Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis |
| title_fullStr |
Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis |
| title_full_unstemmed |
Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis |
| title_sort |
hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis |
| publishDate |
2007 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v73_n6_p873_Lelli http://hdl.handle.net/20.500.12110/paper_00062952_v73_n6_p873_Lelli |
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1768543973877481472 |