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Noncanonical functions of glucocorticoids: A novel role for glucocorticoids in performing multiple beneficial functions in endometrial stem cells.
Park, Se-Ra; Kim, Seong-Kwan; Kim, Soo-Rim; Kim, Doojin; Kim, Kun-Woo; Hong, In-Sun; Lee, Hwa-Yong.
Afiliação
  • Park SR; Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, Republic of Korea.
  • Kim SK; Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, Republic of Korea.
  • Kim SR; Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, Republic of Korea.
  • Kim D; Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, Republic of Korea.
  • Kim KW; Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, Republic of Korea.
  • Hong IS; Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, Republic of Korea.
  • Lee HY; Department of Surgery, Gachon University Gil Medical Center, Gachon University School of Medicine, Incheon, Korea.
Cell Death Dis ; 12(6): 612, 2021 06 12.
Article em En | MEDLINE | ID: mdl-34120144
Chronic stress has a negative impact on many fertility-related functions; thus, the recent decline in female fertility seems to be at least partially associated with increased stress. The secretion of glucocorticoids is a typical endocrine response to chronic stress and indirectly reduces uterine receptivity through the hypothalamus-pituitary-gonadal (HPG) axis. However, in addition to its well-known canonical role, the direct effects of chronic stress-induced glucocorticoids on various uterine functions and their underlying molecular mechanisms are complex and have not yet been revealed. Recent studies have found that resident stem cell deficiency is responsible for the limited regenerative potential of the endometrium (the innermost lining of the uterine cavity) during each menstrual cycle, which subsequently increases infertility rates. In this context, we hypothesized that stress-induced glucocorticoids directly damage endometrial stem cells and consequently negatively affect endometrial reconstruction, which is important for uterine receptivity. In addition to its well-known canonical roles, we identified for the first time that cortisol, the most abundant and potent glucocorticoid in humans, directly suppresses the multiple beneficial functions (self-renewal, transdifferentiation, and migratory potential) of human endometrial stem cells through its functional receptor, glucocorticoid receptor (GR). Glucocorticoids inhibit well-known survival signals, such as the PI3K/Akt and FAK/ERK1/2 pathways. More importantly, we also found that immobilization of stress-induced glucocorticoids suppresses the various beneficial functions of tissue resident stem cells in vivo. To the best of our knowledge, this is the first study to investigate the direct effects of glucocorticoids on the regenerative capacity of endometrial stem cells, and the findings will facilitate the development of more promising therapeutic approaches to increase female fertility.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco / Endométrio / Glucocorticoides Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Cell Death Dis Ano de publicação: 2021 Tipo de documento: Article País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco / Endométrio / Glucocorticoides Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Cell Death Dis Ano de publicação: 2021 Tipo de documento: Article País de publicação: Reino Unido