The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Mechanism of abnormal production of adrenal androgens in patients with adrenocortical adenomas and carcinomas.
Abstract
The production of adrenal androgens can be modulated by the activities of steroidogenic enzymes and by the electron transfer system, NADPH-cytochrome P450 reductase (Red) and cytochrome b5 (b5), both of which have been shown to increase 17,20-lyase activity in vitro. To clarify the mechanism of diminished secretion of adrenal androgens in patients with adrenocortical adenoma and Cushing's syndrome and of excess secretion in patients with adrenocortical carcinoma, we investigated the enzymatic activities of cytochrome P45017 alpha, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), and Red as well as the content of b5 in five adenomas, three carcinomas, and two normal adrenal glands. An in vitro enzyme assay using a microsomal fraction of the tissues indicated that all the tumors had almost the same degree of 17 alpha-hydroxylase activities as the normal adrenals. However, the relative activity ratio of 17,20-lyase to 17 alpha-hydroxylase of the three adenomas was markedly diminished, and 3 beta-HSD activity was apparently lower in the three carcinomas. The messenger RNA concentrations of P45017 alpha were similar in all tumors, whereas those of 3 beta-HSD were markedly lower in the carcinomas than in other tissues. Both the content of b5 and the activity of Red were significantly lower in the adenomas. These results suggest that low concentrations of adrenal androgens in patients with adrenocortical adenomas are mainly due to low 17,20-lyase activity, which may be explained in part by a lower content of b5 and Red. In addition, high concentrations of adrenal androgens in patients with adrenocortical carcinoma are mainly due to the diminished activity of 3 beta-HSD.
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“However, studies of DNA from affected patients revealed that the CYP11A1 gene encoding P450scc was normal21,22,23,24), and in 1995 this disease was more properly termed 'congenital lipoid adrenal hyperplasia (lipoid CAH)', and it was caused by mutations in the gene encoding StAR3,25).”
From Congenital lipoid adrenal hyperplasia (2014) · cites this paper as [23]
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Adrenarche—physiology, biochemistry and human disease
Auchus, R. J., & Rainey, W. E. (2004) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2003.01858.x · Cited by 296
Dissecting human adrenal androgen production
Rainey, W. E., Carr, B. R., Sasano, H., Suzuki, T., & Mason, J. I. (2002) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(02)00609-4 · Cited by 268
Kim, C. J., Lin, L., Huang, N., Quigley, C. A., AvRuskin, T. W., Achermann, J. C., & Miller, W. L. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2330 · Cited by 139
A review of mechanistic studies on aromatase (CYP19) and 17α-hydroxylase-17,20-lyase (CYP17)
Akhtar, M., Wright, J. N., & Lee-Robichaud, P. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.11.003 · Cited by 128
Congenital lipoid adrenal hyperplasia
Kim, C. J. (2014) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2014.19.4.179 · Cited by 105
Metadata
- Authors
- Sakai, Y., Yanase, T., Hara, T., Takayanagi, R., Haji, M., & Nawata, H.
- Affiliations
- Kyushu University (JP)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1994-01
- Volume
- 78
- Issue
- 1
- Pages
- 36-40
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1980462887
- Cited by
- 34
- References
- 18
- Citations by year
- 2025: 2 · 2021: 1 · 2019: 3 · 2018: 2 · 2015: 2 · 2014: 1
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (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
- adrenal androgens, adrenal adenoma, adrenocortical carcinoma, Cushing's syndrome, 17,20-lyase, 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase, NADPH-cytochrome P450 reductase, cytochrome b5, steroidogenic enzymes, enzyme activity, messenger RNA expression, adrenal microsomes
- MeSH terms
- Adenoma, Adrenal Cortex Neoplasms, Adrenal Glands, Adult, Androgens, Carcinoma, Child, Child, Preschool, Female, Humans, Infant, Microsomes, Middle Aged, NADPH-Ferrihemoprotein Reductase, RNA, Messenger, Steroid 17-alpha-Hydroxylase, 3-Hydroxysteroid Dehydrogenases, Cytochromes b5
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