Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH
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 corticos...
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todo:paper_1355008X_v7_n3_p331_Morita2023-10-03T16:10:17Z Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH Morita, H. Cozza, E.N. Zhou, M.-Y. Gomez-Sanchez, E.P. Romero, D.G. Gomez-Sanchez, C.E. 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 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. Fil:Cozza, E.N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Romero, D.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_1355008X_v7_n3_p331_Morita |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Morita, H. Cozza, E.N. Zhou, M.-Y. Gomez-Sanchez, E.P. Romero, D.G. Gomez-Sanchez, C.E. |
| author_facet |
Morita, H. Cozza, E.N. Zhou, M.-Y. Gomez-Sanchez, E.P. Romero, D.G. Gomez-Sanchez, C.E. |
| author_sort |
Morita, H. |
| title |
Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH |
| title_short |
Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH |
| title_full |
Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH |
| title_fullStr |
Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH |
| title_full_unstemmed |
Regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: Decrease enzymatic activity induced by ACTH |
| title_sort |
regulation of the 11β-hydroxysteroid dehydrogenase in the rat adrenal: decrease enzymatic activity induced by acth |
| url |
http://hdl.handle.net/20.500.12110/paper_1355008X_v7_n3_p331_Morita |
| work_keys_str_mv |
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