Sulfation of tibolone metabolites by human postmenopausal liver and small intestinal sulfotransferases (SULTs)

  title={Sulfation of tibolone metabolites by human postmenopausal liver and small intestinal sulfotransferases (SULTs)},
  author={M. Wang and Christopher C. Ebmeier and John R. Olin and Robert J. Anderson},
Sulfation is a major pathway in humans for the biotransformation of steroid hormones and structurally related therapeutic agents. Tibolone is a synthetic steroid used for the treatment for climacteric symptoms and postmenopausal osteoporosis. Sulfation inactivates the hydroxylated metabolites, 3alpha-hydroxytibolone (3alpha-OH-tibolone) and 3beta-hydroxytibolone (3beta-OH-tibolone), and contributes to the regulation of tissue responses to tibolone. We detected SULT1A1, SULT1A3, SULT1E1 and… Expand
Effect of tibolone and its principal metabolites (3α- and 3β-hydroxy, 3α-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue
This very significant inhibitory effect of tibolone and its principal metabolites on the enzyme involved in E2biosynthesis in the human breast provides interesting perspectives to study the biological responses of these compounds in trials with breast cancer patients. Expand
Selective Tissue Distribution of Tibolone Metabolites in Mature Ovariectomized Female Cynomolgus Monkeys after Multiple Doses of Tibolone
It is concluded that tibolone metabolites show a unique tissue-specific distribution pattern explaining the tissue effects in monkeys and the clinical effects in postmenopausal women. Expand
Levels of Tibolone and Estradiol and their Nonsulfated and Sulfated Metabolites in Serum, Myometrium, and Vagina of Postmenopausal Women Following Treatment for 21 Days With Tibolone, Estradiol, or Estradiol Plus Medroxyprogestrone Acetate
Serum and tissue levels of endogenous and exogenous E1, E2, and E 1S were markedly increased 20 hours after E2 or E2 + MPA; the percentage of E1S and tissue:serum ratios were not affected. Expand
Bioequivalence Studies of Tibolone in Premenopausal Women and Effects on Expression of the Tibolone‐Metabolizing Enzyme AKR1C (Aldo‐Keto Reductase) Family Caused by Estradiol
The authors did not find significant differences in pharmacokinetic parameters between the 2 formulations, but metabolite formation was different from reports in postmenopausal women, which might result from changes in AKR1C family expression by patient estrogen status. Expand
Pharmacokinetic Parameters of Tibolone and Metabolites in Plasma, Urine, Feces, and Bile from Ovariectomized Cynomolgus Monkeys after a Single Dose or Multiple Doses of Tibolone
Tibolone had different metabolite patterns in plasma, urine, feces, and bile in monkeys, and the bile contributed to the metabolite pattern in feces after multiple doses. Expand
Curcuminoids Inhibit Multiple Human Cytochromes P450, UDP-Glucuronosyltransferase, and Sulfotransferase Enzymes, whereas Piperine Is a Relatively Selective CYP3A4 Inhibitor
It is predicted that a p.o. administered curcuminoid/piperine combination is most likely to inhibit CYP3A, CYP2C9, UGT, and SULT metabolism within the intestinal mucosa. Expand
Pharmacokinetic Parameters of Sulfated Tibolone Metabolites in Postmenopausal Women after Single and Multiple Doses of Tibolone
After multiple treatment cycles with different doses of tibolone, metabolite levels at 10 h were dose‐related and levels of di‐S metabolites were three‐ to fivefold higher than after a single dose. Expand
Interactions of Endoxifen and other major metabolites of Tamoxifen with human sulfotransferases SULT2A1, SULT1E1, and SULT1A1*1 : implications for the therapeutic action and toxicity of Tamoxifen
Recommended Citation Squirewell, Edwin Jermaine. "Interactions of Endoxifen and other major metabolites of Tamoxifen with human sulfotransferases SULT2A1, SULT1E1, and SULT1A1*1 : implications forExpand
The estrogenic component of tibolone reduces adiposity in female aromatase knockout mice
The study in the ArKO mouse has confirmed the efficacy of tibolone as a hormone therapy to reduce adipose tissue accumulation after menopause and also shows that aromatization of tIBolone is not required to elicit these estrogenic effects. Expand
Roles of human sulfotransferases in genotoxicity of carcinogens using genetically engineered umu test strains
The present results suggest that the generated test strains are valuable tools in order to elucidate the role of SULT enzymes in the bioactivation of chemicals to environmental carcinogens. Expand


Sulfation of tibolone and tibolone metabolites by expressed human cytosolic sulfotransferases
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 moodExpand
Sulfation of iodothyronines by recombinant human liver steroid sulfotransferases.
  • X. Li, R. J. Anderson
  • Chemistry, Medicine
  • Biochemical and biophysical research communications
  • 1999
SULT2A1 may contribute more to iodothyronine sulfation than previously suspected, and potential roles of both steroid sulfotransferases in the enhanced sulfation of nonthyroidal illnesses and fetal development invite further investigation. Expand
Human thyroid phenol sulfotransferase enzymes 1A1 and 1A3: activities in normal and diseased thyroid glands, and inhibition by thyroid hormones and phytoestrogens.
Inhibition of these SULT activities by the exogenous phytoestrogens daidzein and genistein, with a potential decrease in iodide reutilization, presents another mechanism through which these compounds may adversely affect human thyroid function. Expand
Tibolone: a compound with tissue specific inhibitory effects on sulfatase
The tissue specific inhibition pattern of sulfatase activity by tibolone and its metabolites suggest that tiblone could be protective against development of mammary carcinomas, whereas it retains favorable estrogenic effects on bone. Expand
Tibolone: a steroid with a tissue-specific mode of action
  • H. Kloosterboer
  • Medicine, Biology
  • The Journal of Steroid Biochemistry and Molecular Biology
  • 2001
It is concluded that tibolone acts as a tissue-specific compound by mediating its effects via steroid receptors and enzymatic pathways, and avoids stimulation of the endometrium and breast tissue. Expand
Thermostable (SULT1A1) and thermolabile (SULT1A3) phenol sulfotransferases in human osteosarcoma and osteoblast cells.
The results indicate that SULT 1A1 and SULT1A3 are present in human osteosarcoma and mature osteoblast cell lines, and that the characteristics of the osteosARcoma cell SULTs are similar to those expressed in other human tissues. Expand
Human jejunal estrogen sulfotransferase and dehydroepiandrosterone sulfotransferase: immunochemical characterization of individual variation.
There was not a significant correlation between levels of immunoreactive protein for the two enzymes, indicating that EST and DHEA ST in the human jejunum are regulated independently. Expand
Human estrogen sulfotransferase (SULT1E1) pharmacogenomics: gene resequencing and functional genomics
It is raised the possibility that genetically determined variation in SULT1E1‐catalyzed estrogen sulfation might contribute to the pathophysiology of estrogen‐dependent diseases as well as variation in the biotransformation of exogenously administered estrogens. Expand
Human gastrointestinal sulfotransferases: identification and distribution.
The results suggest that xenobiotics may regulate human small intestinal STs, and demonstrate high variation of small intestine sulfation activities compared with human liver activities among different donors. Expand
Expression profiling of human sulfotransferase and sulfatase gene superfamilies in epithelial tissues and cultured cells.
The expression profile of SULT 1A1, 1A3, 1E1, and 2B1a/b suggests that one or more of these isoforms may be involved in the cutaneous sulfoconjugation of minoxidil and cholesterol. Expand