Mitotane Has an Estrogenic Effect on Sex Hormone-Binding Globulin and Corticosteroid-Binding Globulin in Humans
Abstract
Context Side effects of mitotane (o,p'-DDD) have suggested estrogenic effects. Objective The objective of the study was to explore o,p'-DDD potential estrogenic effect on SHBG and corticosteroid-binding globulin (CBG). Design Human hepatoma cell lines (HepG2), lacking estrogen receptor (ER)-alpha, and Hep89, stably transfected by ERalpha, were used. Setting The study was conducted at an academic research laboratory and medical center. Patients and other participants The study included 10 male patients with recurrent adrenal carcinoma, receiving mitotane (4-6.5 g daily) for more than 6 months. Main outcome measures The main outcome measures were SHBG/CBG mRNA levels measured by real-time PCR, culture medium SHBG/CBG concentrations measured by specific immunoassays, and transient transfection experiments with human SHBG proximal promoter reporter constructs. Results Increased serum SHBG and CBG concentrations, which exceeded normal male limits, were observed in most mitotane-treated patients. In the HepG2 cell line, 17beta-estradiol (E2) or o,p'-DDD treatment had no effect on mRNA or SHBG/CBG concentrations. In contrast, in the Hep89 cell line, E2 increased concentrations of SHBG (r = 0.44, P Conclusions Mitotane increased SHBG/CBG gene expression and liver production by mechanisms requiring the presence of ERalpha.
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Use of mitotane in treatment of adrenal carcinoma is associated with an increase in plasma SHBG levels.
“Similarly, the use of mitotane in the treatment of adrenal carcinoma, is associated with an increase in plasma SHBG levels [103].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [103]
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- Authors
- Nader, N., Raverot, G., Emptoz-Bonneton, A., Déchaud, H., Bonnay, M., Baudin, E., & Pugeat, M.
- Affiliations
- Inserm (FR)
- Institut Gustave Roussy (FR)
- ORCID
- Raverot, Gérald
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2006-06
- Volume
- 91
- Issue
- 6
- Pages
- 2165-2170
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2106503032
- Cited by
- 89
- References
- 2
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 1 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 8 · 2014: 7 · 2013: 3 · 2012: 8
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McGill University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- mitotane, estrogenic effects, sex hormone-binding globulin, corticosteroid-binding globulin, estrogen receptor alpha, adrenocortical carcinoma, hepatoma cell lines, estradiol, adverse drug reactions
- MeSH terms
- Adrenal Gland Neoplasms, Estradiol, Humans, Liver, Male, Mitotane, Promoter Regions, Genetic, RNA, Messenger, Sex Hormone-Binding Globulin, Transcortin, Transcription, Genetic, Tumor Cells, Cultured, Antineoplastic Agents, Hormonal, Estrogen Receptor alpha
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