Relationship between Ca2+ and cAMP as second messengers in ACTH-induced cortisol production in bovine adrenal fasciculata cells
In adrenal fasciculata cells stimulated by ACTH, Ca2+ and cAMP play indispensable roles as second messengers in cortisol production. However, whether their second messengers cooperatively or independently participate in steroid production remains unclear. We focused on the roles of Ca2+ and cAMP in...
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The Japan Endocrine Society
2023-12-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/70/12/70_EJ23-0253/_html/-char/en |
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| author | Masahiko Kutsukake Naoko Kuwabara Yoshikazu Miyate Kenzo Kudo Shoko Goto Eiichi Taira Eiichi Tachikawa |
| author_facet | Masahiko Kutsukake Naoko Kuwabara Yoshikazu Miyate Kenzo Kudo Shoko Goto Eiichi Taira Eiichi Tachikawa |
| author_sort | Masahiko Kutsukake |
| collection | DOAJ |
| description | In adrenal fasciculata cells stimulated by ACTH, Ca2+ and cAMP play indispensable roles as second messengers in cortisol production. However, whether their second messengers cooperatively or independently participate in steroid production remains unclear. We focused on the roles of Ca2+ and cAMP in cortisol production in bovine adrenal fasciculata cells stimulated by ACTH for a relatively short period (1 h). Incubation of the cells with 100 pM ACTH in Ca2+-containing (normal) medium for 1 h increased cortisol production without affecting cAMP content. In contrast, treatment of the cells with the peptide at a higher concentration (1 nM) significantly augmented both cortisol production and cAMP content. However, ACTH did not increase either of them in the Ca2+-free medium. ACTH rapidly increased the intracellular free Ca2+ concentration ([Ca2+]i) in the normal medium, but did not influence [Ca2+]i in the Ca2+-free medium, indicating that ACTH caused Ca2+ influx into the cells. ACTH-induced Ca2+ influx and cortisol production were suppressed by a voltage-sensitive L-type Ca2+ channel blocker but not by a T-type, N-type, or P-type Ca2+ channel blocker. In contrast, dibutyryl cAMP, a cell-permeable cAMP analog, greatly enhanced cortisol production in the normal or Ca2+-free medium and slowly caused Ca2+ influx into the cells. These results strongly suggest that Ca2+, as a second messenger, is more critical than cAMP for cortisol production. However, both second messengers jointly participate in the production in adrenal fasciculata cells stimulated by ACTH. |
| format | Article |
| id | doaj-art-8ebc60b91051407187344957013c451f |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-8ebc60b91051407187344957013c451f2025-01-22T06:25:09ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402023-12-0170121123113010.1507/endocrj.EJ23-0253endocrjRelationship between Ca2+ and cAMP as second messengers in ACTH-induced cortisol production in bovine adrenal fasciculata cellsMasahiko Kutsukake0Naoko Kuwabara1Yoshikazu Miyate2Kenzo Kudo3Shoko Goto4Eiichi Taira5Eiichi Tachikawa6Unaduki Pharmacy, Toyama 938-0862, JapanDepartment of Endocrine & Neural Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanDepartment of Pharmacology, School of Medicine, Iwate Medical University, Iwate 028-3694, JapanDivision of Clinical Pharmaceutics and Pharmacy Practice, Department of Clinical Pharmacy, School of Pharmacy, Iwate Medical University, Iwate 028-3694, JapanTakizawa Laboratory Administration Section, Radioactive Waste Management Division, Japan Radioisotope Association, Iwate 020-0603, JapanDepartment of Pharmacology, School of Medicine, Iwate Medical University, Iwate 028-3694, JapanDepartment of Endocrine & Neural Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanIn adrenal fasciculata cells stimulated by ACTH, Ca2+ and cAMP play indispensable roles as second messengers in cortisol production. However, whether their second messengers cooperatively or independently participate in steroid production remains unclear. We focused on the roles of Ca2+ and cAMP in cortisol production in bovine adrenal fasciculata cells stimulated by ACTH for a relatively short period (1 h). Incubation of the cells with 100 pM ACTH in Ca2+-containing (normal) medium for 1 h increased cortisol production without affecting cAMP content. In contrast, treatment of the cells with the peptide at a higher concentration (1 nM) significantly augmented both cortisol production and cAMP content. However, ACTH did not increase either of them in the Ca2+-free medium. ACTH rapidly increased the intracellular free Ca2+ concentration ([Ca2+]i) in the normal medium, but did not influence [Ca2+]i in the Ca2+-free medium, indicating that ACTH caused Ca2+ influx into the cells. ACTH-induced Ca2+ influx and cortisol production were suppressed by a voltage-sensitive L-type Ca2+ channel blocker but not by a T-type, N-type, or P-type Ca2+ channel blocker. In contrast, dibutyryl cAMP, a cell-permeable cAMP analog, greatly enhanced cortisol production in the normal or Ca2+-free medium and slowly caused Ca2+ influx into the cells. These results strongly suggest that Ca2+, as a second messenger, is more critical than cAMP for cortisol production. However, both second messengers jointly participate in the production in adrenal fasciculata cells stimulated by ACTH.https://www.jstage.jst.go.jp/article/endocrj/70/12/70_EJ23-0253/_html/-char/enca2+campcortisol productionadrenal fasciculata cellsecond messenger |
| spellingShingle | Masahiko Kutsukake Naoko Kuwabara Yoshikazu Miyate Kenzo Kudo Shoko Goto Eiichi Taira Eiichi Tachikawa Relationship between Ca2+ and cAMP as second messengers in ACTH-induced cortisol production in bovine adrenal fasciculata cells Endocrine Journal ca2+ camp cortisol production adrenal fasciculata cell second messenger |
| title | Relationship between Ca2+ and cAMP as second messengers in ACTH-induced cortisol production in bovine adrenal fasciculata cells |
| title_full | Relationship between Ca2+ and cAMP as second messengers in ACTH-induced cortisol production in bovine adrenal fasciculata cells |
| title_fullStr | Relationship between Ca2+ and cAMP as second messengers in ACTH-induced cortisol production in bovine adrenal fasciculata cells |
| title_full_unstemmed | Relationship between Ca2+ and cAMP as second messengers in ACTH-induced cortisol production in bovine adrenal fasciculata cells |
| title_short | Relationship between Ca2+ and cAMP as second messengers in ACTH-induced cortisol production in bovine adrenal fasciculata cells |
| title_sort | relationship between ca2 and camp as second messengers in acth induced cortisol production in bovine adrenal fasciculata cells |
| topic | ca2+ camp cortisol production adrenal fasciculata cell second messenger |
| url | https://www.jstage.jst.go.jp/article/endocrj/70/12/70_EJ23-0253/_html/-char/en |
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