Sulfation of tibolone and tibolone metabolites by expressed human cytosolic sulfotransferases
Abstract
Tibolone is an important therapeutic agent used in the treatment of menopausal symptoms in many countries and has beneficial effects on menopausal and postmenopausal vasomotor, bone, vaginal and mood symptoms without affecting the endometrial, breast or cardiovascular systems. The rapid metabolism of tibolone to active metabolites including 3alpha-OH-tibolone, 3beta-OH-tibolone and Delta(4)-tibolone may be important in its tissue-specific effects. Sulfation also has a major role in the metabolism and regulation of the tissue-specific activity of tibolone and its metabolites. The ability of seven major expressed human sulfotransferase (SULT) isoforms to sulfate tibolone and its three metabolites was examined. Expressed human SULT2A1 was capable of sulfating tibolone and all three metabolites with the highest affinity for 3alpha-OH-tibolone. SULT1E1 conjugated both 3-OH-tibolone metabolites and tibolone itself slightly. SULT2B1b sulfated both 3-OH metabolites but not tibolone or Delta(4)-tibolone. SULT isoforms 1A1, 1A3, 1B1 and 1C1 did not demonstrate detectable activity. Sulfation of tibolone and its metabolites by human tissue cytosols was analyzed to determine whether the pattern of tibolone sulfation corresponded to the known expression of SULT isoforms in each tissue. The tissue-specific effects of tibolone may be regulated in part by the inactivation of tibolone and its metabolites by specific human SULT isoforms.
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The formation of distinct di-sulfates is described for the synthetic androgen tibolone and cholesterol.
“The formation of distinct di-sulfates is described for the synthetic androgen tibolone (Falany et al., 2004) and cholesterol (Cook et al., 2009).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Falany et al., 2004
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Intracrine androgen biosynthesis, metabolism and action revisited
Schiffer, L., Arlt, W., & Storbeck, K.-H. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.08.016 · Cited by 217 · see citing works
“The formation of distinct di-sulfates is described for the synthetic androgen tibolone (Falany et al., 2004) and cholesterol (Cook et al., 2009).”
Function and organization of the human cytosolic sulfotransferase (SULT) family
Coughtrie, M. W. H. (2016) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2016.05.005 · Cited by 142 · see citing works
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Self-citationJin, Y., Duan, L., Lee, S. H., Kloosterboer, H. J., Blair, I. A., & Penning, T. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809465200 · Cited by 50 · see citing works
- Authors
- Falany, J. L., Macrina, N., & Falany, C. N.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Falany, Josie L
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 88
- Issue
- 4-5
- Pages
- 383-391
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2074918060
- Cited by
- 56
- References
- 28
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2021: 4 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 1
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- tibolone, sulfation, sulfotransferase, SULT2A1, SULT1E1, SULT2B1b, drug metabolism, tissue-specific metabolism, hormone replacement therapy
- MeSH terms
- Adrenal Glands, Cytosol, Humans, Intestines, Isoenzymes, Kinetics, Liver, Norpregnenes, Mass Spectrometry, Sulfates, Tissue Distribution, Sulfotransferases
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