2-hydroxyestrone and Neoplasms

Endogenous estradiol metabolism results in metabolic products that are still capable of exerting various biological, partially estrogen-antagonistic actions. This indicates that the effects of estradiol in carcinogenesis may depend on individual variations of metabolic breakdown of estradiol. The aim of this paper is to review and discuss the available data relating to stimulatory and inhibitory properties of estradiol metabolites on carcinogenesis. Results of main D-ring metabolites and main A-ring metabolites are presented. There are indications that the endogenous production of growth influencing estradiol metabolites may be elevated in neoplasias. Some results in this respect are available for stimulating tumor growth for the D-ring metabolite 16-hydroxyestrone and the A-ring metabolites 4-hydroxyestrone and 4-hydroxyestradiol. Inhibitory effects exist for the A-ring metabolite 2-methoxyestradiol (2-ME). So far, only a few metabolites have been studied closely for their influence on carcinogenesis. There is also a dearth of data on the intracellular metabolism of estradiol in neoplastic tissues. Knowledge of the metabolites may reveal new approaches to diagnosis and treatment of malignant diseases. 2-ME has already shown actions in pharmacological dosages which led already to a first trial to prove its suitability for treating human breast cancer.

Topics: 2-Methoxyestradiol; Anticarcinogenic Agents; Estradiol; Estriol; Estrogens, Catechol; Female; Humans; Hydroxyestrones; Molecular Structure; Neoplasms

In vertebrates, the glucuronidation of small lipophilic agents is catalyzed by the endoplasmic reticulum UDP-glucuronosyltransferases (UGTs). This metabolic pathway leads to the formation of water-soluble metabolites originating from normal dietary processes, cellular catabolism, or exposure to drugs and xenobiotics. This classic detoxification process, which led to the discovery nearly 50 years ago of the cosubstrate UDP-glucuronic acid (19), is now known to be carried out by 15 human UGTs. Characterization of the individual gene products using cDNA expression experiments has led to the identification of over 350 individual compounds that serve as substrates for this superfamily of proteins. This data, coupled with the introduction of sophisticated RNA detection techniques designed to elucidate patterns of gene expression of the UGT superfamily in human liver and extrahepatic tissues of the gastrointestinal tract, has aided in understanding the contribution of glucuronidation toward epithelial first-pass metabolism. In addition, characterization of the UGT1A locus and genetic studies directed at understanding the role of bilirubin glucuronidation and the biochemical basis of the clinical symptoms found in unconjugated hyperbilirubinemia have uncovered the structural gene polymorphisms associated with Crigler-Najjar's and Gilbert's syndrome. The role of the UGTs in metabolism and different disease states in humans is the topic of this review.

Topics: Autoimmunity; Chromosome Mapping; Glucuronides; Glucuronosyltransferase; Humans; Hyperbilirubinemia; Neoplasms; Steroids; Terminology as Topic

Gynecological cancers are among the most common in women and are directly related to a variety of hormonal factors. One potential risk factor associated with developing a gynecological malignancy is the ratio of two hormone metabolites, 2-Hydroxyestrone (2-HE) and 16alpha-Hydroxyestrone (16alpha-HE). A number of botanical constituents such as indoles, flavonoids, and resveratrol have been shown to have a favorable effect on the metabolic pathways that affect this ratio. The present study was designed to evaluate if a multi-nutrient supplement containing targeted botanical constituents would affect the 2-HE/16 alpha-HE ratio in middle-aged women.. A retrospective analysis was performed on 76 female patients (mean age 54 years) who received 2-HE/16 alpha-HE ratio assessments at two separate time points. The ratio assessment was part of standard care for women who presented with risk indicators associated with a high proliferative state. All patients who completed pre and post assessments were included. Sixty-five of the patients received a multi-nutrient supplement, Lucentia Peak, during the study period. Eleven patients chose not to take the supplement, but did receive ratio assessments at similar time points as the treatment group, allowing for between group comparisons. Paired t-tests were used to compare the changes in the 2-HE and 16alpha-HE measures as well as their ratio, both within groups and between groups.. The results demonstrated a significant increase in the 2-HE/16alpha-HE ratio in the treated group (pre 0.38 to post 0.57, p<0.0001), and was significantly different (p=0.02) compared to the change in the control group (pre 0.65 to post 0.64). This change appears to be mediated primarily by an increase in the 2-HE level. Individually, 54 patients given Lucentia Peak had increased ratios while 11 patients had a decrease. In the control group, 3 patients had an increase in their ratio and 8 patients had a decrease.. The results demonstrated that women receiving the Lucentia Peak multi-nutrient supplement had significant increases in their 2-HE:16alpha-HE ratio, which appears to be mediated primarily by increasing the 2-HE levels. These results suggest further research on phytonutrients that might positively affect estrogen metabolism is warranted.

Topics: Case-Control Studies; Dietary Supplements; Female; Follow-Up Studies; Humans; Hydroxyestrones; Middle Aged; Neoplasms; Risk Factors

Topics: Animals; Carcinogens; Estrogens; Female; Humans; Hydroxyestrones; Mutagens; Neoplasms