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Abstract:

Different cytochromes P450 are involved in steroid biosynthesis. These cytochromes have heme as the prosthetic group. We previously reported that ACTH, an activator of glucocorticoid biosynthesis in adrenal, requires heme biosynthesis for a maximal response. In the present study, we investigated the effect of ACTH, and the effect of two activators of the adrenal mineralocorticoid synthesis, endothelin-1 and low sodium diet on 5-aminolevulinate-synthase (ALA-s) mRNA. ALA-s is the rate-limiting enzyme in heme biosynthesis. It was found that infusion of rats with ACTH for 1 h caused an increase of adrenal ALA-s mRNA and activity accompanied by an increase in plasma corticosterone. CYP21, a cytochrome involved in the synthesis of both corticosterone and aldosterone, was not modified at the RNA level in adrenal glands by 1 h of ACTH infusion. Consistently, infusion of endothelin-1 for 1 h increased ALA-s mRNA and aldosterone content in adrenal gland without modifying CYP21 mRNA levels. To study if ALA-s is also regulated by the main physiological stimuli that increase adrenal mineralocorticoid secretion, we fed rats with low salt diet for 2 or 15 days. Low salt diet treatment increased adrenal gland ALA-s mRNA levels. On the other hand, the rapid stimulation of ALA-s mRNA by ACTH which acts through cyclic AMP was confirmed in H295R human adrenocortical cells, the only human adrenal cell line that has a steroid secretion pattern and regulation similar to primary cultures of adrenal cells. Our findings suggest that the acute activation of adrenal steroidogenic cytochromes by trophic hormones involves an increase in heme biosynthesis which will favor the production of active cytochromes. © 2007 Elsevier Inc. All rights reserved.

Registro:

Documento: Artículo
Título:Induction of 5-aminolevulinate synthase by activators of steroid biosynthesis
Autor:Martini, C.N.; Romero, D.G.; Yanes, L.L.; Vila, M.d.C.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon 2, Ciudad Universitaria, 1428 Buenos Aires, Argentina
Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, United States
Facultad de Ciencias Exactas, Químicas y Naturales, Universidad de Morón, Buenos Aires, Argentina
Palabras clave:ACTH; Ala-synthase (ALA-s); Cytochrome P450 21-hydroxylase (CYP21); Endothelin; H295R human adrenocortical cells; Low sodium diet; Rat adrenal; Steroid biosynthesis; 5 aminolevulinate synthase; corticosterone; corticotropin; cyclic AMP; cytochrome P450; endothelin 1; messenger RNA; mineralocorticoid; steroid; steroid 21 monooxygenase; adrenal cell; animal experiment; animal tissue; article; controlled study; enzyme activation; enzyme induction; heme synthesis; hormonal regulation; human; human cell; male; nonhuman; protein expression; rat; sodium restriction; steroidogenesis; 5-Aminolevulinate Synthetase; Adrenal Cortex; Adrenocorticotropic Hormone; Aldosterone; Animals; Cell Line; Corticosterone; Diet, Sodium-Restricted; Endothelin-1; Enzyme Induction; Heme; Humans; Male; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA; Rattus
Año:2007
Volumen:81
Número:1
Página de inicio:19
Página de fin:25
DOI: http://dx.doi.org/10.1016/j.lfs.2007.04.020
Título revista:Life Sciences
Título revista abreviado:Life Sci.
ISSN:00243205
CODEN:LIFSA
CAS:5 aminolevulinate synthase, 9037-14-3; corticosterone, 50-22-6; corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; cyclic AMP, 60-92-4; cytochrome P450, 9035-51-2; steroid 21 monooxygenase, 9029-68-9; 5-Aminolevulinate Synthetase, EC 2.3.1.37; Adrenocorticotropic Hormone, 9002-60-2; Aldosterone, 52-39-1; Corticosterone, 50-22-6; Endothelin-1; Heme, 14875-96-8; RNA, 63231-63-0
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00243205_v81_n1_p19_Martini

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Citas:

---------- APA ----------
Martini, C.N., Romero, D.G., Yanes, L.L. & Vila, M.d.C. (2007) . Induction of 5-aminolevulinate synthase by activators of steroid biosynthesis. Life Sciences, 81(1), 19-25.
http://dx.doi.org/10.1016/j.lfs.2007.04.020
---------- CHICAGO ----------
Martini, C.N., Romero, D.G., Yanes, L.L., Vila, M.d.C. "Induction of 5-aminolevulinate synthase by activators of steroid biosynthesis" . Life Sciences 81, no. 1 (2007) : 19-25.
http://dx.doi.org/10.1016/j.lfs.2007.04.020
---------- MLA ----------
Martini, C.N., Romero, D.G., Yanes, L.L., Vila, M.d.C. "Induction of 5-aminolevulinate synthase by activators of steroid biosynthesis" . Life Sciences, vol. 81, no. 1, 2007, pp. 19-25.
http://dx.doi.org/10.1016/j.lfs.2007.04.020
---------- VANCOUVER ----------
Martini, C.N., Romero, D.G., Yanes, L.L., Vila, M.d.C. Induction of 5-aminolevulinate synthase by activators of steroid biosynthesis. Life Sci. 2007;81(1):19-25.
http://dx.doi.org/10.1016/j.lfs.2007.04.020