Immunohistochemical study of cytochrome b5 in human adrenal gland and in adrenocortical adenomas from patients with Cushing’s syndrome
Open accessAbstract
Cytochrome b5, a component of the electron transfer system increases the relative activity of 17,20-lyase to 17alpha-hydroxylase of P450c17 in vitro. In the present study, immunohistochemical analysis of cytochrome b5 was performed in the human adrenal gland and in adrenocortical adenomas from patients with Cushing's syndrome. In the human adrenal gland, cytochrome b5 was stained in all three adrenocortical layers but the staining was most remarkable in the zona reticularis. All of the adenomas were composed mainly of compact cells, which exhibited immunoreactive staining for cytochrome b5 as well as for P450c17 and 3beta-hydroxysteroid dehydrogenase (3beta-HSD). The distribution of b5 in the adenomas was correlated with that of P450c17 rather than with that of 3beta-HSD. The immunoreactive staining for cytochrome b5 appeared to be more prominent in the two adenomas that produced relatively high concentrations of adrenal androgens than in adenomas that produced low concentrations of adrenal androgens. These results immunohistochemically support the functional association of b5 with androgen production through interaction with P450c17 and the previous finding that higher concentrations of cytochrome b5 are associated with greater production of adrenal androgens in adrenocortical adenomas from patients with Cushing's syndrome.
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Cites
Hildebrandt, A. G., & Estabrook, R. W. (1971) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(71)90186-x · Cited by 557 · see citing works
Purification and Properties of Rat Liver Microsomal Stearyl Coenzyme A Desaturase
Strittmatter, P., Spatz, L., Corcoran, D., Rogers, M. J., Setlow, B., & Redline, R. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.11.4565 · Cited by 469 · see citing works
17α-Hydroxylase/17,20 lyase deficiency: from clinical investigation to molecular definition
YANASE, T., SIMPSON, E. R., & WATERMAN, M. R. (1991) · Endocrine Reviews · doi:10.1210/edrv-12-1-91 · Cited by 390 · see citing works
Self-citationExpression of Bovine 17α-Hydroxylase Cytochrome P-450 cDNA in Nonsteroidogenic (COS 1) Cells
Zuber, M. X., Simpson, E. R., & Waterman, M. R. (1986) · Science · doi:10.1126/science.3535074 · Cited by 388 · see citing works
The role of cytochrome b5 in the biosynthesis of androgens by human P450c17
Katagiri, M., Kagawa, N., & Waterman, M. R. (1995) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1995.1173 · Cited by 223 · see citing works
Nakajin, S., Shinoda, M., Haniu, M., Shively, J. E., & Hall, P. F. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)43191-7 · Cited by 212 · see citing works
Control of adrenal androgen secretion.
Parker, L. N., & Odell, W. (1980) · Endocrine reviews · doi:10.1210/edrv-1-4-392 · Cited by 184 · see citing works
Yanagibashi, K., & Hall, P. F. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)83930-3 · Cited by 171 · see citing works
Kagimoto, M., Winter, J. S. D., Kagimoto, K., Simpson, E. R., & Waterman, M. R. (1988) · Molecular Endocrinology · doi:10.1210/mend-2-6-564 · Cited by 161 · see citing works
MATTESON, K. J., PICADO-LEONARD, J., CHUNG, B.-C., MOHANDAS, T. K., & MILLER, W. L. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-63-3-789 · Cited by 160 · see citing works
Cytochrome b5 stimulates purified testicular microsomal cytochrome P-450 (C21 side-chain cleavage)
Onoda, M., & Hall, P. F. (1982) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(82)90850-6 · Cited by 126 · see citing works
Studies on methemoglobin reductase
Fumio, K. U. M. A., Prough, R. A., & Masters, B. S. S. (1976) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(76)90113-2 · Cited by 74 · see citing works
Immunohistochemical study of cytochrome P-45017α in human adrenocortical disorders
Sasano, H., Mason, J. I., & Sasano, N. (1989) · Human Pathology · doi:10.1016/0046-8177(89)90174-3 · Cited by 68 · see citing works
Self-citationTamburini, P. P., & Gibson, G. G. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)43934-2 · Cited by 64 · see citing works
Shinzawa, K., Kominami, S., & Takemori, S. (1985) · PubMed · Cited by 63 · see citing works
Aoyama, T., Nagata, K., Yamazoe, Y., Kato, R., Matsunaga, E., Gelboin, H. V., & Gonzalez, F. J. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.14.5425 · Cited by 63 · see citing works
Cytochrome b5 as Electron Donor for Oxy‐cytochrome P‐450
Noshiro, M., Ullrich, V., & Omura, T. (1981) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1981.tb05367.x · Cited by 63 · see citing works
Immunolocalization of 3β-hydroxysteroid dehydrogenase in human adrenal cortex and in its disorders
Sasano, H., Mason, J. L., Sasano, N., & Nagura, H. (1990) · Endocrine Pathology · doi:10.1007/bf02915624 · Cited by 61 · see citing works
Self-citationKyoko, S., Shiro, K., & Takemori, S. (1985) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(85)90263-2 · Cited by 52 · see citing works
Sakai, Y., Yanase, T., Takayanagi, R., Nakao, R., Nishi, Y., Haji, M., & Nawata, H. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.76.5.8496319 · Cited by 46 · see citing works
Self-citationSakai, Y., Yanase, T., Hara, T., Takayanagi, R., Haji, M., & Nawata, H. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.78.1.8288710 · Cited by 34 · see citing works
Self-citationSakai, Y., Yanase, T., Hara, T., Takayanagi, R., Haji, M., & Nawata, H. (1994) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1994.tb02469.x · Cited by 27 · see citing works
Self-citationMcCarthy, J. L., & Waterman, M. R. (1988) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(88)90031-3 · Cited by 18 · see citing works
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Miller, W. L., & Auchus, R. J. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0013 · Cited by 2,458 · see citing works
Neurosteroids: biosynthesis and function of these novel neuromodulators
Compagnone, N. A., & Mellon, S. H. (2000) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1999.0188 · Cited by 820 · see citing works
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Miller, W. L. (2005) · Endocrinology · doi:10.1210/en.2005-0096 · Cited by 324 · see citing works
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Mellon, S. H., & Vaudry, H. (2001) · International review of neurobiology · doi:10.1016/s0074-7742(01)46058-2 · Cited by 211 · see citing works
Suzuki, T., Sasano, H., Takeyama, J., Kaneko, C., Freije, W. A., Carr, B. R., & Rainey, W. E. (2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01144.x · Cited by 199 · see citing works
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Flück, C. E., Miller, W. L., & Auchus, R. J. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030143 · Cited by 173 · see citing works
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Pandey, A. V., & Miller, W. L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414673200 · Cited by 165 · see citing works
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Self-citationThe molecular basis of premature adrenarche: an hypothesis
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Kempná, P., Hirsch, A., Hofer, G., Mullis, P. E., & Flück, C. E. (2010) · Endocrinology · doi:10.1210/en.2010-0093 · Cited by 35 · see citing works
Assessment of the ability of type 2 cytochrome b5 to modulate 17,20-lyase activity of human P450c17
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Pattison, J. C., Abbott, D. H., Wendy Saltzman, A., Nguyen, A. D., Henderson, G. L., Jing, H., Pryce, C. R., Allen, A. J., Conley, A. J., & Bird, I. M. (2004) · Endocrinology · doi:10.1210/en.2004-0689 · Cited by 32 · see citing works
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Benign cortisol‐secreting adrenocortical adenomas produce small amounts of androgens
Kamenický, P., Houdoin, L., Ferlicot, S., Salenave, S., Brailly, S., Droupy, S., Méduri, G., Sasano, H., Suzuki, T., Young, J., et al. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02810.x · Cited by 24 · see citing works
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Lamb, D. C., Kaderbhai, N., Kanamarlapudi, V., Kelly, D. E., Kelly, S. L., & Kaderbhai, M. A. (2001) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2001.2566 · Cited by 20 · see citing works
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Brock, B. J., & Waterman, M. R. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1557 · Cited by 19 · see citing works
Nakamura, Y., Suzuki, T., & Sasano, H. (2007) · Endocrine Journal · doi:10.1507/endocrj.k07e-001 · Cited by 9 · see citing works
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Miller, W. L., & Auchus, R. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.3.1346 · Cited by 9 · see citing works
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Smith, S. S. (2003) · CRC Press eBooks · doi:10.1201/9780203508169.ch1 · Cited by 9 · see citing works
Santi, D., Granata, A. R. M., Pignatti, E., Trenti, T., Roli, L., Bozic, R., Zaza, S., Pacchioni, C., Rochira, V., Carani, C., et al. (2016) · Endocrine · doi:10.1007/s12020-016-1055-x · Cited by 6 · see citing works
Ziaja, J., Cholewa, K., Mazurek, U. M., & Cierpka, L. (2008) · PubMed · Cited by 5 · see citing works
Cushing's Syndrome after Hemodialysis for 21 Years
Mise, K., Ubara, Y., Sumida, K., Hiramatsu, R., Hasegawa, E., Yamanouchi, M., Hayami, N., Suwabe, T., Hoshino, J., Sawa, N., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2766 · Cited by 4 · see citing works
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Abe, I., Yamazaki, Y., Higashi, A., Ochi, K., Kubo, K., Fujita, Y., Takeshita, K., Wada, T., Mitsuoka, R., Yamashita, Y., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1624396 · Cited by 1 · see citing works
Self-citationThe Adrenal Cortex and its Disorders
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Yubisui, T., Takabayashi, T., Takahashi, F., Fujiwara, S., & Kawamura, K. (2004) · The Journal of Biochemistry · doi:10.1093/jb/mvh027
Self-citation
- Authors
- YANASE, T., SASANO, H., YUBISUI, T., SAKAI, Y., TAKAYANAGI, R., & NAWATA, H.
- Affiliations
- Kyushu University (JP)
- Tohoku University (JP)
- University of Kochi (JP)
- Venue
- Endocrine Journal
- Publisher
- Japan Endocrine Society
- Published
- 1998
- Volume
- 45
- Issue
- 1
- Pages
- 89-95
- ISSN
- 0918-8959 (ISSN-L)
- 1348-4540
- OpenAlex
- W2069032561
- Semantic Scholar
- fe6fc62106c6336d34755bf48d9ef1ff9e55b2b6
- Cited by
- 54
- References
- 23
- Citations by year
- 2025: 1 · 2021: 3 · 2018: 1 · 2016: 1 · 2015: 1 · 2012: 3
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- cytochrome b5, Cushing's syndrome, adrenal adenoma, adrenal gland, P450c17, 3β-hydroxysteroid dehydrogenase, adrenal androgen production, zona reticularis, 17,20-lyase, 17α-hydroxylase, steroidogenesis
- MeSH terms
- Adenoma, Adrenal Cortex, Adrenal Cortex Neoplasms, Cushing Syndrome, Humans, Immunohistochemistry, Male, Middle Aged, Steroid 17-alpha-Hydroxylase, Tissue Distribution, 3-Hydroxysteroid Dehydrogenases, Zona Reticularis, Cytochromes b5
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