problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl9550problendo-9550Research ArticleОбзорыReviewsМетилирование эстрогенов, ожирение и рак молочной железыMethylation of estrogens, obesity and breast cancerhttps://orcid.org/0000-0001-8022-9291ЧагайНаталья БорисовнаChagayNatalia B.

доктор медицинских наук

MD, PhD

chagaynb@gmail.comhttps://orcid.org/0000-0003-1316-5245МкртумянАшот МусаеловичMkrtumyanAshot M.

д.м.н., проф.

MD, PhD, Professor

vagrashot@mail.ru<p>Ставропольский краевой клинический консультативно-диагностический центр</p>Россия<p>Stavropol Regional Clinical Consultative and Diagnostic Center</p>Russian Federation<p>ФГБОУ ВО &laquo;Московский&nbsp;государственный медико-стоматологический университет им. А.И. Евдокимова&raquo; Минздрава России</p>Россия<p>Moscow State University of Medicine and Dentistry named after A.I. Evdokimov</p>Russian Federation201806102018644244251Copyright &#x00A9; Чагай Н.Б., Мкртумян А.М., 20182018Чагай Н.Б., Мкртумян А.М.Chagay N.B., Mkrtumyan A.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/9550

Метилирование катехолэстрогенов осуществляется при участии фермента катехол-О-метилтрансферазы, синтез и активность которого кодируется геном COMT. Подавление экспрессии гена COMT формирует риск развития эстрогензависимых опухолей. Одним из факторов, определяющих статус общего метилирования в организме, является ожирение.

Существует два основных типа жировой ткани, отличающихся по своим функциональным и метаболическим характеристикам, а также микроскопическому строению: белая (white adipose tissue — WAT) и бурая (brown adipose tissue — BAT) жировая ткань. Процесс липолиза WAT контролируется гормончувствительной липазой, зависимой в большой степени от катехоламинов. BAT — специализированный тип жировой ткани, основной функцией которого является производство тепла. Активация катехоламинами центральных и периферических β3-адренергических рецепторов является пусковым фактором термогенеза зрелой ВАТ.

У больных с ожирением развивается гипоксия жировой ткани, дисфункция WAT и BAT. Наблюдается «отбеливание» бурых адипоцитов, проявляющееся деградацией митохондриального аппарата. Адренергическая стимуляция термогенеза ВАТ оказывается невостребованной. Перенаправление стимуляции катехоламинами гормончувствительной липазы на WAT, повышение потребности к усилению экспрессии СОМТ — таковы вероятные последствия измененного метаболизма ВАТ.

Эстрогены являются естественными модуляторами липолиза (путем избирательного влияния на активность гормончувствительной липазы) и регуляторами термогенеза ВАТ. Ожирение сопровождается развитием гиперэстрогении вследствие усиления синтеза эстрона. Однако период постменопаузы характеризуется снижением общей массы и активности ВАТ. Роль ВАТ в прогрессии или торможении роста эстрогензависимой опухолевой ткани в пременопаузальном и постменопаузальном возрасте не изучена и представляет интерес для исследователей. Обсуждается возможная связь между активностью бурых адипоцитов и экспрессией гена СОМТ в контексте риска развития доброкачественной дисплазии и рака молочной железы.

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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The authors declare that there are no conflicts of interest present.