Disease relevance of Catecholestrone

• Urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio and risk of breast cancer in postmenopausal women [1].
• Therefore, infusion of 2-hydroxyestrone cannot be used in the differential diagnosis of hypothalamic and tumoral hyperprolactinemia [2].
• We conclude that: 1) 2-Hydroxyestrone does not suppress PRL levels in patients with prolactinomas [2].

Psychiatry related information on Catecholestrone

• Physical activity has been associated with reduced breast cancer risk, potentially via hormonal pathways, and high urinary excretion of 2-hydroxyestrone (2-OH E(1)) relative to 16alpha-hydroxyestrone (16alpha-OH E(1)) also has been associated with reduced breast cancer risk [3].

High impact information on Catecholestrone

• The nonuterotropic natural estrogen 2-hydroxyestrone administered to normal young women results in a prompt and profound suppression of serum prolactin in most of the subjects [4].
• Suppression of prolactin secretion in normal young women by 2-hydroxyestrone [4].
• In the presence of quinalizarin, a potent catechol O-methyltransferase inhibitor which reduces the O-methylation of the steroid, 10(-7) M and 10(-8) M 2-hydroxyestrone markedly suppresses the growth and proliferation of the cells [5].
• In the flaxseed group, the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone was positively correlated with urinary lignan excretion (r = 0.579, P = 0.02) [6].
• 2) 2-Hydroxyestrone does not diminish PRL levels in patients with suprasellar tumors and hyperprolactinemia [2].

Chemical compound and disease context of Catecholestrone

• The alternative product of estrogen metabolism, 2-hydroxyestrone, does not exhibit estrogenic properties in breast tissue, and lower values of the ratio 2-hydroxyestrone:16alpha-hydroxyestrone (2:16) in urine may be an endocrine biomarker for greater breast cancer risk [7].
• Increased oxidation of estrone to 2-hydroxyestrone (2HE) relative to 16alpha-hydroxyestrone (16HE) has been hypothesized to reduce breast cancer risk, but little is known about the effect of physical activity and body size in relation to the ratio of 2HE and 16HE in women [8].
• Women with high, medium, and low levels of physical activity were compared for menstrual function, physical characteristics, and urinary and serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol-17 beta, and 2-hydroxyestrone [9].
• Previous studies from this laboratory have suggested that 2-hydroxyestrone is protective against breast cancer, whereas the other principal metabolite, 16 alpha-hydroxyestrone, and the lesser metabolite quantitatively, 4-hydroxyestrone, are potent carcinogens [10].
• Previous research indicated that some organochlorine-based pesticides elevated the production of 16 alpha-hydroxyestrone relative to 2-hydroxyestrone in ER+ MCF-7 breast cancer cells while phytochemicals like indole-3-carbinol reduced this ratio [11].

Biological context of Catecholestrone

• A double isotope derivative determination technique was developed to investigate the excretion of 2-hydroxyestrone inhuman menstrual cycle [12].
• Excretion of 2-hydroxyestrone in urine throughout human pregnancies [13].
• The investigation of 2-hydroxyestrone and total estrogens at regular intervals throughout several pregnancies, showed that the excretion of 2-hydroxyesterone generally reached a maximum during the second trimester, while the excretion of the total estrogens steadily increased up to parturition [13].
• In a study designed to evaluate the kinetics of catechol estrogen formation from plasma estrone in vivo, we obtained evidence that the red blood cell (RBC) enzyme, catechol-O-methyl transferase, catalyzes the transformation of 2-hydroxyestrone to 2-methoxyestrone [14].
• Injection of 100 micrograms 2-hydroxyestrone (2OHE1) at various times on the morning of proestrus into normal 4-day-cycling rats results in abolition of the preovulatory LH surge in a number of animals tested [15].

Anatomical context of Catecholestrone

• Compared on the basis of wet weight of tissues (250 mg), the conversion of estradiol to 2-hydroxyestrogens (2-hydroxyestradiol and 2-hydroxyestrone) was 0.8% in the frontal cortex, 1.0% in the hypothalamus, 2.1% in the pituitary, and 7.8% in the liver [16].
• NADPH-dependent oxidation of E(2) by liver microsomes from ACI and Sprague-Dawley rats produced several metabolites of which 2-hydroxyestradiol (2-OH-E(2)), estrone (E(1)), and 2-hydroxyestrone (2-OH-E(1)) were predominant [17].
• Inhibition of the preovulatory LH surge after a catecholestrogen (2-hydroxyestrone) antiserum injection in the third ventricle of cycling female rats [18].
• Interestingly, the quantity of 2-hydroxyestrone found in kidney microsomes of the hamster represented 26% of the total amount of metabolites formed, whereas in liver microsomes, only 9% of the overall metabolism resulted in the formation of 2-hydroxyestrone [19].
• Tissue-selective effects of continuous release of 2-hydroxyestrone and 16alpha-hydroxyestrone on bone, uterus and mammary gland in ovariectomized growing rats [20].

Associations of Catecholestrone with other chemical compounds

• The amounts of 2-hydroxyestrone excreted during menstrual cycle varied between 10 (proliferation phase) and 60 mug/24 h urine (ovulatory peak), which is comparable to that of estriol, supposed hitherto to be the main excretion product of estrogen metabolism [12].
• However, when estrone was the substrate, CYP1A1 formed more 4-hydroxyestrone than 15alpha- or 6alpha-hydroxyestrone, with 2-hydroxyestrone as the major metabolite [21].
• The principal metabolite of 2-hydroxyestrone, 2-methoxyestrone, given at noon of proestrus, significantly augments the magnitude of the preovulatory prolactin rise possibly by inhibiting the formation of endogenous 2-hydroxyestrogens in the brain [22].
• The o-quinone of 2-hydroxyestrone isomerized to two QMs; a QM stabilized by one alkyl substituent in the B ring, 2-OHE-QM1 (3-hydroxy-1-(10),3(4),5(6)-oestratrien-2,17-dione) and one having two alkyl substituents on the methylene group in the C ring, 2-OHE-QM2 (2-hydroxy-1(2),4(5),9(10)-oestratrien-3,17-dione) [23].
• Catechol estrogens, such as 2-hydroxyestriol, 2-hydroxyestradiol, and 2-hydroxyestrone, inhibit human liver dihydropteridine reductase noncompetitively with Ki values ranging from 1.5 to 4.6 X 10(-6)M [24].

Gene context of Catecholestrone

• UGT1A3, when expressed in COS cells has a relative molecular mass of 55 kDa and is active in the glucuronidation of estrone and 2-hydroxyestrone [25].
• The apparent induction of CYP1A2 was mirrored by a 66% increase in the urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio in response to I3C [26].
• Using microsome preparation (from HK293 cell expressing monkey UGT1A01), the apparent K(m) values were 13, 5 and 6 microM for the conjugation of estradiol, 2-hydroxyestradiol and 2-hydroxyestrone, respectively, and were very similar to the values obtained with human UGT1A1 [27].
• In animals synchronized with exogenous estradiol, 2-hydroxyestrone universally induced a long delay in the prolactin surge [22].
• Additionally, when 2-hydroxyestrone was used as a substrate, the estrogen-induced renal carcinoma exhibited only 8.6% of the COMT activity found in the normal kidney [28].

Analytical, diagnostic and therapeutic context of Catecholestrone

• The plasma metabolic clearance rate (MCRp) of 2-hydroxyestrone was measured in normal young adults by two methods: infusion of unlabeled 2-OHE1 to equilibrium with radioimmunoassay of plasma 2-OHE1 levels, and infusion of [3H]2-OHE1 to equilibrium with measurement of chromatographically purified plasma [3H]2-OHE1 [29].
• A new ELISA kit for measuring urinary 2-hydroxyestrone, 16alpha-hydroxyestrone, and their ratio: reproducibility, validity, and assay performance after freeze-thaw cycling and preservation by boric acid [30].
• 2-Hydroxyestrone and 16 alpha-hydroxyestrone were measured by enzyme immunoassay, and the estrogen metabolite ratio (EMR; 2-hydroxyestrone:16 alpha-hydroxyestrone) was computed [31].
• Male rats treated for 7 days with either 2-hydroxyestradiol, 4-hydroxyestradiol or 2-hydroxyestrone had significantly lower striatal dihydroxy phenylacetic acid (DOPAC) levels when compared to the control group [32].
• Other outcome measures include: the ratio of urinary 2-hydroxyestrone: 16alpha-hydroxyestrone (an estrogen metabolite ratio that may be associated with risk for breast cancer), weight, body mass index, total fat mass, and body fat distribution (waist:hip circumference ratio, DEXA scan, and abdominal fat measured by computed tomography) [33].

References