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Abstract:

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.

Registro:

Documento: Artículo
Título:Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis
Autor:Lelli, S.M.; Ceballos, N.R.; Mazzetti, M.B.; Aldonatti, C.A.; San Martín de Viale, L.C.
Filiación:Laboratorio de Disturbios Metabolicos por Xenobioticos, Salud Humana y Medio Ambiente (DIMXSA), Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, C1428EGA Ciudad Auton. Buenos Aires, Argentina
Laboratorio de Endocrinología Comparada, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, C1428EGA Ciudad Auton Buenos Aires, Argentina
Palabras clave: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
Año:2007
Volumen:73
Número:6
Página de inicio:873
Página de fin:879
DOI: http://dx.doi.org/10.1016/j.bcp.2006.11.012
Título revista:Biochemical Pharmacology
Título revista abreviado:Biochem. Pharmacol.
ISSN:00062952
CODEN:BCPCA
CAS:allylisopropylacetamide, 299-78-5; corticosterone, 50-22-6; corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; glucose, 50-99-7, 84778-64-3; griseofulvin, 126-07-8; hexachlorobenzene, 118-74-1, 55600-34-5; phosphoenolpyruvate carboxykinase (GTP), 9013-08-5; reduced nicotinamide adenine dinucleotide, 58-68-4; Corticosterone, 50-22-6; Endocrine Disruptors; Hexachlorobenzene, 118-74-1; Phosphoenolpyruvate Carboxykinase (ATP), EC 4.1.1.49; Porphyrins; Receptors, Glucocorticoid
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v73_n6_p873_Lelli

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Citas:

---------- APA ----------
Lelli, S.M., Ceballos, N.R., Mazzetti, M.B., Aldonatti, C.A. & San Martín de Viale, L.C. (2007) . Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis. Biochemical Pharmacology, 73(6), 873-879.
http://dx.doi.org/10.1016/j.bcp.2006.11.012
---------- CHICAGO ----------
Lelli, S.M., Ceballos, N.R., Mazzetti, M.B., Aldonatti, C.A., San Martín de Viale, L.C. "Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis" . Biochemical Pharmacology 73, no. 6 (2007) : 873-879.
http://dx.doi.org/10.1016/j.bcp.2006.11.012
---------- MLA ----------
Lelli, S.M., Ceballos, N.R., Mazzetti, M.B., Aldonatti, C.A., San Martín de Viale, L.C. "Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis" . Biochemical Pharmacology, vol. 73, no. 6, 2007, pp. 873-879.
http://dx.doi.org/10.1016/j.bcp.2006.11.012
---------- VANCOUVER ----------
Lelli, S.M., Ceballos, N.R., Mazzetti, M.B., Aldonatti, C.A., San Martín de Viale, L.C. Hexachlorobenzene as hormonal disruptor-studies about glucocorticoids: Their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis. Biochem. Pharmacol. 2007;73(6):873-879.
http://dx.doi.org/10.1016/j.bcp.2006.11.012