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Abstract:

Patients with ectopic ACTH syndrome often develop hypertension and hypokalemic alkalosis with an abnormal increase in the ratio of plasma cortisol to cortisone, indicating that 11β-hydroxysteroid dehydrogenase (11βHSD) activity is inhibited. Inhibition of 11βHSD allows access of cortisol or corticosterone to the mineralocorticoid receptor where it act as a mineralocorticoid. Two isozymes, 11βHSD-1 and 11βHSD-2, have been cloned and characterized. The rat adrenal expresses the mRNAs for 11βHSD-2 and, in lesser amounts, 11βHSD-1. We investigated the effect of ACTH on the 11 11βHSD-2 activity in the rat adrenal. Rat adrenal cells zone fasciculata (ZF) were dispersed and incubated separately with increasing concentrations of ACTH for 90 min, and secretion of corticosterone (B) and 11- dehydrocorticosterone (A) in the media was measured by enzyme-linked immunoabsorbent assays (ELISA). The conversion of [ 3H]B to [ 3H]A in the presence of 0.5 mM NAD + was evaluated in microsomes prepared from dispersed cells preincubated for 30 min with cyanoketone and metyrapone followed by incubation for 30 min with the same inhibitors, with and without 10 nM ACTH. The dispersed cells of the ZF produced significant amounts of A which increased with ACTH. The basal B/A ratio was 0.97 ± 0.05. ACTH caused a concentration-dependent increase in the ratio of B/A with a maximum ratio of 9.58 ± 0.20. ACTH also inhibited the conversion of [ 3H]B to [ 3H]A in microsomes in which endogenous B production was inhibited by cyanoketone and metyrapone. ACTH did not change the K(m) for B conversion, but the V(max) was reduced significantly (1.73 ± 0.43 pmol/min · mg protein), indicating that ACTH suppressed the 11βHSD-2 in a noncompetitive fashion. Dibutyryl cyclic AMP (dcAMP) also produced a concentration-dependent increase in the B/A ratio, but various concentrations of calcium did not affect the enzyme activity. In summary, adrenal cells treated with ACTH results in a significant increase in the ratio of B/A in the ZF owing a noncompetitive inhibition of the 11βHSD-2 via the ACTH receptor.

Registro:

Documento: Artículo
Título:Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH
Autor:Morita, H.; Cozza, E.N.; Zhou, M.-Y.; Gomez-Sanchez, E.P.; Romero, D.G.; Gomez-Sanchez, C.E.
Filiación:Div. Endocrinol., Diabet., Metab., Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO, United States
Endocrinol. Sect. and Res. Service, Harry S. Truman Mem. Vet. Hospital, Columbia, MO, United States
Dept. of Vet. Biomedical Sciences, University of Missouri, Columbia, MO, United States
Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
PRHOM-CONICET, 1428 Buenos Aires, Argentina
Research Service, Harry S. Truman Mem. Vet. Hospital, University of Missouri, 800 Hospital Drive, Columbia, MO 65201, United States
Palabras clave:11β-hydroxysteroid dehydrogenase; ACTH; Ectopic ACTH syndrome; Rat adrenals; 11beta hydroxysteroid dehydrogenase; corticotropin receptor; adrenal gland; animal cell; article; corticosterone release; ectopic corticotropin production; enzyme localization; enzyme regulation; nonhuman; priority journal; rat; zona fasciculata; 11-beta-Hydroxysteroid Dehydrogenases; Adrenocorticotropic Hormone; Animals; Calcium; Corticosterone; Depression, Chemical; Enzyme-Linked Immunosorbent Assay; Hydroxysteroid Dehydrogenases; Kinetics; Male; Rats; Rats, Sprague-Dawley; Zona Fasciculata
Año:1997
Volumen:7
Número:3
Página de inicio:331
Página de fin:335
Título revista:Endocrine
Título revista abreviado:Endocrine
ISSN:1355008X
CODEN:EOCRE
CAS:11beta hydroxysteroid dehydrogenase, 9041-46-7; 11-beta-Hydroxysteroid Dehydrogenases, 1.1.1.146; Adrenocorticotropic Hormone, 9002-60-2; Calcium, 7440-70-2; Corticosterone, 50-22-6; Hydroxysteroid Dehydrogenases, 1.1.-
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1355008X_v7_n3_p331_Morita

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Citas:

---------- APA ----------
Morita, H., Cozza, E.N., Zhou, M.-Y., Gomez-Sanchez, E.P., Romero, D.G. & Gomez-Sanchez, C.E. (1997) . Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH. Endocrine, 7(3), 331-335.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1355008X_v7_n3_p331_Morita [ ]
---------- CHICAGO ----------
Morita, H., Cozza, E.N., Zhou, M.-Y., Gomez-Sanchez, E.P., Romero, D.G., Gomez-Sanchez, C.E. "Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH" . Endocrine 7, no. 3 (1997) : 331-335.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1355008X_v7_n3_p331_Morita [ ]
---------- MLA ----------
Morita, H., Cozza, E.N., Zhou, M.-Y., Gomez-Sanchez, E.P., Romero, D.G., Gomez-Sanchez, C.E. "Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH" . Endocrine, vol. 7, no. 3, 1997, pp. 331-335.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1355008X_v7_n3_p331_Morita [ ]
---------- VANCOUVER ----------
Morita, H., Cozza, E.N., Zhou, M.-Y., Gomez-Sanchez, E.P., Romero, D.G., Gomez-Sanchez, C.E. Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH. Endocrine. 1997;7(3):331-335.
Available from: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1355008X_v7_n3_p331_Morita [ ]