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Role of SIRT1 and Progesterone Resistance in Normal and Abnormal Endometrium.

Publication ,  Journal Article
Kim, TH; Young, SL; Sasaki, T; Deaton, JL; Schammel, DP; Palomino, WA; Jeong, J-W; Lessey, BA
Published in: J Clin Endocrinol Metab
February 17, 2022

CONTEXT: Progesterone resistance, a known pathologic condition associated with a reduced cellular response to progesterone and heightened estrogen responses, appears to have a normal physiologic role in mammalian reproduction. The molecular mechanism responsible for progesterone resistance in normal and abnormal endometrium remains unclear. OBJECTIVE: To examine the roles of sirtuin-1 (SIRT1) in normal endometrium as well as endometrium associated with infertility and endometriosis, as an epigenetic modulator associated with progesterone resistance. METHODS: SIRT1 expression was examined by Western blot, quantitative real-time polymerase chain reaction, and immunohistochemistry in mouse uterus and human endometrium. Mice with uterine specific Sirt1 overexpression were developed to examine SIRT1's role in endometrial function and endometriosis development. EX-527, a SIRT1 inhibitor, and SRT1720, a SIRT1 agonist, were also used to evaluate SIRT1 effect on endometriosis. RESULTS: In normal healthy women, endometrial SIRT1 is expressed only during menses. SIRT1 was dramatically overexpressed in the endometrium from women with endometriosis in both the epithelium and stroma. In mice, SIRT1 is expressed at the time of implantation between day 4.5 and 5.5 of pregnancy. Overexpression of SIRT1 in the mouse uterus leads to subfertility due to implantation failure, decidualization defects and progesterone resistance. SIRT1 overexpression in endometriotic lesions promotes worsening endometriosis development. EX-527 significantly reduced the number of endometriotic lesions in the mouse endometriosis model. CONCLUSIONS: SIRT1 expression and progesterone resistance appears to play roles in normal endometrial functions. Aberrant SIRT1 expression contributes to progesterone resistance and may participate in the pathophysiology of endometriosis. SIRT1 is a novel and targetable protein for the diagnosis as well as treatment of endometriosis and the associated infertility seen in this disease.

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Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

February 17, 2022

Volume

107

Issue

3

Start / End Page

788 / 800

Location

United States

Related Subject Headings

  • Young Adult
  • Uterine Diseases
  • Sirtuin 1
  • Progesterone
  • Middle Aged
  • Mice, Transgenic
  • Mice
  • Menstruation
  • Infertility, Female
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kim, T. H., Young, S. L., Sasaki, T., Deaton, J. L., Schammel, D. P., Palomino, W. A., … Lessey, B. A. (2022). Role of SIRT1 and Progesterone Resistance in Normal and Abnormal Endometrium. J Clin Endocrinol Metab, 107(3), 788–800. https://doi.org/10.1210/clinem/dgab753
Kim, Tae Hoon, Steven L. Young, Tsutomu Sasaki, Jeffrey L. Deaton, David P. Schammel, Wilder Alberto Palomino, Jae-Wook Jeong, and Bruce A. Lessey. “Role of SIRT1 and Progesterone Resistance in Normal and Abnormal Endometrium.J Clin Endocrinol Metab 107, no. 3 (February 17, 2022): 788–800. https://doi.org/10.1210/clinem/dgab753.
Kim TH, Young SL, Sasaki T, Deaton JL, Schammel DP, Palomino WA, et al. Role of SIRT1 and Progesterone Resistance in Normal and Abnormal Endometrium. J Clin Endocrinol Metab. 2022 Feb 17;107(3):788–800.
Kim, Tae Hoon, et al. “Role of SIRT1 and Progesterone Resistance in Normal and Abnormal Endometrium.J Clin Endocrinol Metab, vol. 107, no. 3, Feb. 2022, pp. 788–800. Pubmed, doi:10.1210/clinem/dgab753.
Kim TH, Young SL, Sasaki T, Deaton JL, Schammel DP, Palomino WA, Jeong J-W, Lessey BA. Role of SIRT1 and Progesterone Resistance in Normal and Abnormal Endometrium. J Clin Endocrinol Metab. 2022 Feb 17;107(3):788–800.
Journal cover image

Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

February 17, 2022

Volume

107

Issue

3

Start / End Page

788 / 800

Location

United States

Related Subject Headings

  • Young Adult
  • Uterine Diseases
  • Sirtuin 1
  • Progesterone
  • Middle Aged
  • Mice, Transgenic
  • Mice
  • Menstruation
  • Infertility, Female
  • Humans