Methylation of estrogens, obesity and breast cancer

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Abstract

Methylation of catechol estrogens is catalyzed by catechol-O-methyltransferase. Synthesis and activity of this enzyme is encoded by the COMT gene. Downregulation of COMT expression is responsible for the risk of developing estrogen-dependent tumors. Obesity is a factor determining the overall methylation status in the body.

There are two main types of adipose tissue differing in their functional and metabolic characteristics, as well as the microscopic structure: white adipose tissue (WAT) and brown adipose tissue (BAT). Lipolysis of WAT is controlled by hormone-sensitive lipase, which depends is catecholamine dependent. BAT is a special type of adipose tissue whose main function is to produce heat. Activation of β3-adrenergic receptors by catecholamines, both at the central and peripheral levels, is the primary mechanism regulating thermogenesis in mature BAT.

Obese patients develop adipose tissue hypoxia, as well as WAT and BAT dysfunction. Adrenergic stimulation of thermogenesis is unclaimed because of «whitening» of brown adipocytes, which manifests itself as degradation of mitochondria. Redirection of stimulation of hormone-sensitive lipase by catecholamines to WAT and the increased need to enhance COMT expression are the potential consequences of modifying the BAT metabolism.

Estrogens are natural modulators of lipolysis (as they selectively affect activity of hormone-sensitive lipase) and regulators of BAT thermogenesis. Obesity is accompanied by elevated synthesis of estrone. However, in postmenopausal women it is characterized by a decrease in the total mass and activity of BAT. The role of BAT in the progression or inhibition of growth of the estrogen-dependent tumor tissue at premenopausal and postmenopausal age has not been studied yet and is of interest to researchers. The possible correlation between the activity of brown adipocytes and the COMT expression level is discussed in the context of the risk of developing benign breast dysplasia and cancer.

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About the authors

Natalia B. Chagay

Stavropol Regional Clinical Consultative and Diagnostic Center

Author for correspondence.
Email: chagaynb@gmail.com
ORCID iD: 0000-0001-8022-9291
SPIN-code: 2323-7791

MD, PhD

Russian Federation, 64, Zapadnyy obkhod, Stavropol, 355029

Ashot M. Mkrtumyan

Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Email: vagrashot@mail.ru
ORCID iD: 0000-0003-1316-5245
SPIN-code: 1980-8700

MD, PhD, Professor

Russian Federation, 20/1, Delegatskaya street, Moscow, 127473

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