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Interactions Between Estrogens and Catechol Amines III. Studies on the Methylation of Catechol Estrogens, Catechol Amines and other Catechols by the Catechol-O-Methyltransferase1 of Human Liver
Abstract
The substrate specificity of the catechol-O-methyltransferase, purified from human liver 380-fold, has been tested with a variety of compounds. Catechol estrogens, as well as catechol amines are methylated to their corresponding monomethyl ethers. The relation of the rates of methylation of catechol estrogens and catechol amines depended on enzyme and substrate concentration; under standard assay conditions, 2-hydroxy-17β-estradiol was the preferred substrate for the enzyme, as compared with epinephrine and other catechols tested. Km-values for 2-hydroxy-17β-estradiol were 15 μm, for 2-hydroxy-estrone 20 μm, for 2-hydroxy-estriol 25 μm and for-hydroxy-estrone 20 μm. For epinephrine and norepinephrine, Km-values of 300 μm and 200 μm, respectively, were obtained. The ratio of formation of the isomeric monomethyl ethers of catechol estrogens varied between 1.3 and 95, depending on the substrate incubated. On the basis of kinetic studies with different enzyme preparations, different inhibitors and different concentrations of the substrates, it is concluded that both catechol estrogens and catechol amines are methylated by the same Catechol-O-methyltransferase. The enzymic methylation of epinephrine was inhibited competitively by 2- and 4-hydroxylated estrogens; the Ki-values were 7.0 μm for 2-hydroxy-17β-estradiol, 8.5 μm for 2-hydroxy-estrone, 12.2 μm for 2-hydroxy-estriol, 50 μm for 4-hydroxy-estrone and, for comparison, 154 μm for the addition of norepinephrine. A non-competitive inhibition was observed with the corresponding isomeric monomethyl ethers. The extent of inhibition not only depended on the relative concentrations of substrates and inhibitors, but also on the concentrations of MgCl2S-adenosylmethionine and enzyme. The results reported here indicate that the enzymic methylation and biological inactivation of neurotransmitters is strongly inhibited by 2-hydroxy-estrogens. These findings are of possible clinical relevance with respect to the regulation of blood pressure under normal and pathological conditions.
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“COMT methylates 2- and 4-hydroxyestrogens, thereby producing the so-called methoxyestrogens [180].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [180]
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Items 201–280 of 280
Ravnikar, V. A., Schiff, I., & Regestein, Q. R. (1983) · CPOBGYN. Clinical perspectives in obstetrics and gynecology · doi:10.1007/978-1-4612-5525-3_12 · Cited by 6
Panek, D. U., Azzaro, A. J., Stitzel, R. E., & Head, R. J. (1987) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00172791 · Cited by 6
“They are excellent substrates for catechol-O-methyltransferase (COMT) from brain (Breuer and Koster 1974) and liver (Ball et al. 1972) exhibiting Km values approximately 10 times lower than those for noradrenaline or dopamine.”
Background2-Hydroxylation of estradiol by rat kidney and lung
Numazawa, M., Kiyono, Y., & Nambara, T. (1980) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(80)90143-0 · Cited by 6
Bates, G. W., Whitworth, N. S., & Jackson, E. (1982) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(16)32332-8 · Cited by 6
Blake, C. A., Fuxé, K., Andersson, K., et al. (1981) · Elsevier eBooks · doi:10.1016/b978-0-08-026864-4.50014-1 · Cited by 6
Suzuki, E., Saegusa, K., Anjo, T., et al. (1993) · Steroids · doi:10.1016/0039-128x(93)90032-i · Cited by 5
New Concepts of Estrogenic Activity: the Role of Metabolites in the Expression of Hormone Action
Fishman, J., & Martucci, C. P. (1980) · Springer eBooks · doi:10.1007/978-94-011-7230-1_5 · Cited by 5
Nakagawa, A., OHUCHI, R., & Yoshizawa, I. (1979) · Journal of Pharmacobio-Dynamics · doi:10.1248/bpb1978.2.365 · Cited by 5
The hypothalamus as an endocrine target organ
Martini, L. (1978) · Palgrave Macmillan UK eBooks · doi:10.1007/978-1-349-03506-9_9 · Cited by 5
Methylation of Catechol Estrogen with Diazomethane
Teranishi, M., Fujii, Y., YAMAZAKI, M., et al. (1983) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.31.3309 · Cited by 5
Majumdar, S., Gupta, U., Chinnasamy, H. V., Laxmipathy, S., & Matheshwaran, S. (2022) · ACS Omega · doi:10.1021/acsomega.2c04555 · Cited by 4
Brand, B. A., Boer, A. J., de Boer, J. N., et al. (2025) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2024.107274 · Cited by 4
The role of dopamine in visual imagery—An experimental pharmacological study
Monzel, M., Karneboge, J., & Reuter, M. (2023) · Journal of Neuroscience Research · doi:10.1002/jnr.25262 · Cited by 4
“Moreover, variation in estrogen across the cycle affects both catechol-O -methyltransferase (COMT) activity (Ball et al., 1972; Harrison & Tunbridge, 2008) and dopamine receptor density (Bazzett & Becker, 1994) and thus dopamine-associated higher cognitive functions (Dubol et al., 2021; Jacobs &…”
BackgroundCatechol-O-methyltransferase activity in erythrocytes of women taking oral contraceptive steroids
Bates, G. W., Edman, C. D., Porter, J. C., et al. (1979) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(79)90020-6 · Cited by 4
Kennedy, J. A. (1991) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00251125 · Cited by 4
Estrogen and catechol amine metabolism: possible interaction during pregnancy
Barnea, E. R., & Naftolin, F. N. (1987) · Journal of Endocrinological Investigation · doi:10.1007/bf03348142 · Cited by 4
Rosenfeld, J. M., & Taguchi, V. T. (1978) · Analytical Letters · doi:10.1080/00032717808059694 · Cited by 4
Parvez, S., Parvez, H. S., & Gripois, D. (1973) · Pharmacological Research Communications · doi:10.1016/s0031-6989(73)80036-0 · Cited by 4
DEVELOPMENTAL ASPECTS OF CATECHOLESTROGEN SYNTHESIS
Hoffman, A. R., POTH, M. A., & Axelrod, J. L. (1981) · Elsevier eBooks · doi:10.1016/b978-0-08-026864-4.50011-6 · Cited by 4
Oestrogen — Androgen Balance in Human Breast and Prostate Cancer
CASTAGNETTA, L. A. M. (1980) · Springer eBooks · doi:10.1007/978-1-4613-3030-1_85 · Cited by 4
Pribluda, V. S., LaVallee, T. M., & Green, S. J. (2002) · Humana Press eBooks · doi:10.1007/978-1-59259-126-8_21 · Cited by 4
Functional and organizational aspects of gonadal steroids in the pig brain
Ellendorff, F., Parvizi, N., ELSAESSER, F., et al. (1979) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(79)90019-0 · Cited by 3
CATECHOL-O-METHYLTRANSFERASE ACTIVITY: ASSAY, DISTRIBUTION AND PHARMACOLOGICAL MODIFICATION
Reenilä, I. (1999) · Työväentutkimus Vuosikirja · Cited by 3
Parvez, S., & Parvez, H. S. (1976) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(76)90147-2 · Cited by 3
Biologic Effects of Natural and Synthetic Estrogens
Quirk, J. G., & Wendel, G. D. (1983) · CPOBGYN. Clinical perspectives in obstetrics and gynecology · doi:10.1007/978-1-4612-5525-3_5 · Cited by 4
Panek, D. U., & Dixon, W. R. (1985) · Brain Research · doi:10.1016/0006-8993(85)90776-0 · Cited by 3
Relation of blood estradiol levels to EEG photic driving in smoking vs. non-smoking normal males
Vogel, W., Broverman, D. M., & Klaiber, E. L. (1985) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(85)90969-1 · Cited by 3
Immunocytochemical localization of catechol estrogen in the rat pituitary gland. I Posterior lobe.
Inoue, K., & Yoshizawa, I. (1986) · ACTA HISTOCHEMICA ET CYTOCHEMICA · doi:10.1267/ahc.19.767 · Cited by 3
“(2) Catechol estrogen-monoaminergic neuron interactions.”
BackgroundMechanism of estrogen action which elicits the anabolic response observed in ruminants
Hancock, D. L. (1989) · ThinkTech (Texas Tech University) · Cited by 3
Cerutti, R. (1982) · Springer eBooks · doi:10.1007/978-3-642-81876-9_47 · Cited by 3
(1976) · Hoppe-Seyler´s Zeitschrift für physiologische Chemie · doi:10.1515/bchm2.1976.357.2.999 · Cited by 3
Creveling, C. R. (1993) · Techniques in the behavioral and neural sciences · doi:10.1016/b978-0-444-81369-5.50017-1 · Cited by 3
Catechol-O-methyltransferase (COMT)
Tassone, G., Carradori, S., Maramai, S., & D’Agostino, I. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-823974-2.00029-2 · Cited by 2
Selective synthesis of 4-methoxyestrogen from 4-hydroxyestrogen
Teranishi, M., Kashihara, M., & Fujii, Y. (2001) · Steroids · doi:10.1016/s0039-128x(00)00236-1 · Cited by 2
Pharmacophore‐Based Methods for Predicting the Inhibition and Induction of Metabolic Enzymes
Kaserer, T., Temml, V., & Schuster, D. (2014) · Methods and principles in medicinal chemistry · doi:10.1002/9783527673261.ch14 · Cited by 2
Fotsis, T., Shah, H. P., H�rk�nen, M., et al. (1987) · Neurochemical Research · doi:10.1007/bf01000234 · Cited by 2
Rodriguez‐Sierra, J. F., & Blake, C. A. (1983) · Proceedings in life sciences · doi:10.1007/978-3-642-69216-1_4 · Cited by 2
The absence of a catechol estrogen effect on blood pressure in the male rat
Chattoraj, S. C. (1983) · Steroids · doi:10.1016/0039-128x(83)90123-x · Cited by 2
In vitro O-methylation of 4-hydroxyestrone monosulfates.
Shimada, K., Yoshiko, Y., & Nambara, T. (1982) · Journal of Pharmacobio-Dynamics · doi:10.1248/bpb1978.5.448 · Cited by 2
Clancey, C. J., Owen-Fett, C., Farley, D. B., et al. (1983) · Journal of Chromatography A · doi:10.1016/s0021-9673(01)88247-9 · Cited by 2
Sagara, Y., Okatani, Y., Kiriyama, T., et al. (1985) · Asia-Oceania Journal of Obstetrics and Gynaecology · doi:10.1111/jog.1985.11.4.597 · Cited by 2
Secondary Amenorrhea and the Menopause
Scommegna, A., & Carson, S. A. (1987) · Springer eBooks · doi:10.1007/978-1-4613-2157-6_17 · Cited by 2
Czarnota, S., Baxter, N. J., Cliff, M. J., Waltho, J. P., Scrutton, N. S., & Hay, S. (2016) · Biomolecular NMR Assignments · doi:10.1007/s12104-016-9720-9 · Cited by 1
Wroolie, T., & Holcomb, M. G. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1526-9_8 · Cited by 1
Estrogen Replacement Therapy and Nocturnal Periodic Limb Movements
Polo‐Kantola, P., Rauhala, E., Erkkola, R., et al. (2001) · Obstetrics and Gynecology · doi:10.1097/00006250-200104000-00013 · Cited by 1
Effect of Catecholestrogens on [3H]-GABA Uptake by Hypothalamic Crude Synaptosomes
Etchegoyen, G. S., & Zotto, H. H. D. (1995) · Archives of Physiology and Biochemistry · doi:10.3109/13813459509047131 · Cited by 1
Thomas, P. J. (1988) · Humana Press eBooks · doi:10.1007/978-1-59259-437-5_7 · Cited by 1
Present status of luteolytic agents in fertility regulation
Dwivedy, I., Ray, S., & Grover, A. (1993) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-7147-1_8 · Cited by 1
Hormonal Mechanisms in Reproduction
Pasqualini, J. R., & Kincl, F. A. (1985) · Elsevier eBooks · doi:10.1016/b978-0-08-019708-1.50005-2 · Cited by 1
Estrogen Therapy and the Brain
Henderson, V. W. (2000) · Elsevier eBooks · doi:10.1016/b978-012453790-3/50022-6 · Cited by 1
Götz, M. E., Künig, G., Riederer, P. F., & Youdim, M. B. H. (1996) · Elsevier eBooks · doi:10.1016/b978-044482529-2/50039-1 · Cited by 1
Krieger, D. T. (1976) · Springer eBooks · doi:10.1007/978-1-4615-8843-6_1 · Cited by 1
Krey, L. C., LIEBERBURG, I., ROY, E., et al. (1979) · Elsevier eBooks · doi:10.1016/b978-0-08-023796-1.50044-x · Cited by 1
AGING, HORMONES AND MENTAL FUNCTIONING
Jarvik, L. F., & WILKINS, J. N. (1978) · Elsevier eBooks · doi:10.1016/b978-1-4832-8322-7.50017-0 · Cited by 1
Bacci, P. A. (2007) · Springer eBooks · doi:10.1007/978-3-540-71097-4_40
Formation of 2-methoxyoestrone from oestrone in human foetal adrenals in vitro
Stárka, L., Šulcová, J., Knüppen, R., et al. (1973) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(73)90075-7
Self-citationReceptors and Mechanism Action of Synthetic Progestogens
Okada, H. (2010) · Asia-Oceania Journal of Obstetrics and Gynaecology · doi:10.1111/j.1447-0756.1981.tb00511.x
Etchegoyen, G. S., & Zotto, H. H. D. (1995) · Archives of Physiology and Biochemistry · doi:10.3109/13813459509047139
Estrogen Modulation of Dopamine Autoreceptors
Bernardi, F., Piccardi, M. P., Bocchetta, A., et al. (1983) · Elsevier eBooks · doi:10.1016/b978-0-08-029804-7.50017-2
Smoking Cessation in a Nicotine Replacement Therapy Randomized Trial
Johnstone, E. C., Elliot, K. M., David, S. P., Walton, R. T., & Munafo, M. R. (2007)
Modulación de los niveles de estrógeno sobre el proceso de toma de decisiones arriesgadas.
Duque, S. P., & Ramírez, J. V. (2015)
Ravnikar, V. A., Schiff, I., & Regestein, Q. R. (1983)
Biosynthese von C19- und C21-Steroiden im Paragangliom und Ph�ochromozytom des Menschen
Rao, G. S., Rao, M. L., Breuer, H., et al. (1978) · Journal of Molecular Medicine · doi:10.1007/bf01477830
Self-citationUrinary catechol estrogens in cycles stimulated by human menopausal gonadotropin
Schinfeld, J. S., Panda, S. K., Chattoraj, S. C., et al. (1983) · Fertility and Sterility · doi:10.1016/s0015-0282(16)47065-2
Clinical data of estrogen's effects in the central nervous system: estrogen and mood
Powers, B. N., Williams, K. E., Wroolie, T., Khaylis, A., & Rasgon, N. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511635700.013
End-organ metabolism of oestrogens
MacLusky, N. J., Clark, C. R., Paden, C. M., & Naftolin, F. N. (1981) · doi:10.1007/978-1-349-81345-2_9 · Cited by 1
Down-regulation of Dopamine Autoreceptors by Estrogens: Physiological Control
Piccardi, M. P., Martis, G., Mulas, S., et al. (1986) · Palgrave Macmillan UK eBooks · doi:10.1007/978-1-349-07431-0_26
Potential modulators and modifiers of estrogenic effects
Hogervorst, E., Henderson, V. W., Gibbs, R. B., & Brinton, R. D. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511635700.012
Geriatric Neurology and Psychiatry
Henderson, V. W. (1999) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-60107-1_24
Estrogenic modulation for making risky decisions
Duque, S. P., Ramírez, J. V., Corredor, F. P., & Pahi, M. R. (2014)
Bio-Lifting and Bio-Resurfacing
Bacci, P. A. (2011) · Springer eBooks · doi:10.1007/978-3-642-17838-2_28
Heffelfinger, S. C. (2005) · CRC Press eBooks · doi:10.1201/9780203503430.ch16
Öney, T., & Kaulhausen, H. (1983) · Springer eBooks · doi:10.1007/978-3-642-69277-2_7
INTERACTION BETWEEN OESTROGENS AND NEUROTRANSMITTERS AT THE HYPOPHYSIAL-HYPOTHALAMIC LEVEL
BREUER, H., & KÖSTER, G. (1975) · Elsevier eBooks · doi:10.1016/b978-0-08-019709-8.50035-6
Self-citationFUNCTIONAL AND ORGANIZATIONAL ASPECTS OF GONADAL STEROIDS IN THE PIG BRAIN
ELLENDORFF, F., PARVIZI, N., ELSAESSER, F., et al. (1979) · Elsevier eBooks · doi:10.1016/b978-0-08-023796-1.50119-5
Ladosky, W., Azambuja, H. M. C., & Schneider, H. T. (1983) · Elsevier eBooks · doi:10.1016/b978-0-08-030771-8.50092-9
(1977) · Elsevier eBooks · doi:10.1016/b978-0-12-510550-7.50010-3
Regulation of Xenobiotic Metabolism in the Liver
Cui, J., & Li, C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.01008-1
閉経後女性のうつ病に対するエストロゲン補充療法とその症例提示(合同シンポジウム:心理ストレスによる身体反応,2009年,第1回日本心身医学5学会合同集会(東京))
大藏, 健., 片岡, 良., & 市村, 三. (2010) · 心身医学 · doi:10.15064/jjpm.50.8_725
Henriksen, K., Jb, B., Es, M., et al. (2005)
Metadata
- Authors
- BALL, P., KNUPPEN, R., HAUPT, M., & BREUER, H.
- Affiliations
- University of Bonn (DE)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1972-04
- Volume
- 34
- Issue
- 4
- Pages
- 736-746
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2010928336
- Cited by
- 280
- References
- 0
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 6.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
- Keywords
- catechol estrogens, epinephrine, norepinephrine, methylation, 2-hydroxyestrone, 4-hydroxyestrone, monomethyl ether, substrate specificity, enzyme kinetics, competitive inhibition, non-competitive inhibition, human liver
- MeSH terms
- Adult, Carbon Isotopes, Catecholamines, Catechols, Chemistry, Chlorides, Cysteine, Dopamine, Epinephrine, Estradiol, Estriol, Estrogens, Estrone, Humans, Kinetics, Liver, Magnesium, Male, Mandelic Acids, Methylation, Methyltransferases, Norepinephrine, S-Adenosylmethionine, Time Factors, Chemical Phenomena
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