Roles of Ca2+ and cyclic AMP as second messengers in cortisol production
Cortisol, an adrenal cortical hormone, is produced from cholesterol in zona fasciculata cells via a stimulation of adrenocorticotropin (ACTH) and is secreted to the blood flow. The elevation of cyclic AMP in the cells is required for the production of cortisol. On the other hand, Ca^2+ influx into t...
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Published in | Japanese Journal of Pharmacology Vol. 82; no. suppl.2; p. 267 |
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Main Authors | , , , , |
Format | Journal Article |
Language | Japanese English |
Published |
The Japanese Pharmacological Society
2000
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Online Access | Get full text |
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Summary: | Cortisol, an adrenal cortical hormone, is produced from cholesterol in zona fasciculata cells via a stimulation of adrenocorticotropin (ACTH) and is secreted to the blood flow. The elevation of cyclic AMP in the cells is required for the production of cortisol. On the other hand, Ca^2+ influx into the cells also seems to play a crucial role in the production. In this study, we investigated the roles of Ca^2+ and cyclic AMP as second messengers and the relationship between them in the cortisol production The production of cortisol in bovine adrenal fasciculata cells induced by ACTH was dependent on the external Ca^2+ concentrations, and the depletion of the Ca^2+ abolished the ACTH-induced cortisol production. The production induced by forskolin, an activator of adenylate cyclase, was also diminished by the external C2+ omission. However, the dibutyryl cyclic AMP-induced production was not affected under the same condition. Alamethicin, which is a Ca^2+ channel-forming peptide, slightly stimulated the cortisol production. On the other hand, the ACTH- and the forskolin-induced production but not the dibutyryl cyclic AMP-induced production were greatly inhibited by alamethicin. The peptide also significantly reduced the ACTH- and the forskolin-induced increases in cyclic AMP level in the cells, but itself did not increase the cyclic AMP level. These results strongly indicate that the presence of extracellular Ca^2+ is essential for the ACTH-induced production of cortisol. However, the direct participation of the Ca^2+ influx into the cells in the production may be much less but the small amount of influx may be indispensable to activate the adenylate cyclase. |
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ISSN: | 0021-5198 1347-3506 |
DOI: | 10.1016/S0021-5198(19)48530-2 |