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Regulation of Serine/Threonine Kinase 4 (STK4) Expression by Estrogen in the Mouse Uterus
Sohyeon Moon,Sangho Lee,Minha Cho,Boreum Song,Miseon Park,Ok-Hee Lee,Hoon Jang,Youngsok Choi 한국동물생명공학회(구 한국동물번식학회) 2017 Reproductive & Developmental Biology(Supplement) Vol.41 No.2
The Hippo signaling pathway is essential for regulating proliferation, differentiation, and apoptosis in mammalian cells. It has been reported that the members of Hippo signaling pathway are highly expressed in mammalian ovaries and uteri. However, the regulatory mechanism of this pathway in the uterus during estrous cycle regulation remains unclear. Serine/Threonine Protein Kinase 4 (STK4) (known as MST1) is a major factor of Hippo signaling pathway. However STK4 in the mouse uterus has not yet been examined. The purpose of our study was to determine the expression of STK4 during the estrous cycle and regulation by estrogen in the mouse uterus. We found that Stk4 mRNA was dynamically expressed in uterine endometrium during the estrous cycle. The expression of Stk4 was significantly increased at the stage of estrus and diestrus among the estrus cycle, whereas its expression was decreased at proestrus and metestrus stages. The localization of Stk4 was highly detected in Luminal epithelial (LE) and Glandular epithelial (GE) in uterine endometrium. In addition, we demonstrated that Estrogen (E2) administration into ovariectomized mice increased the expression of Stk4 in the uterus. The expression of Stk4 by E2 was gradually increased depending on the time up to 6 hours after the treatment and then decreased. Moreover, the treatment the Estrogen receptor inhibitor, ICI 182, 780 (ICI), before E2 injection significantly reduced the alleviation of Stk4 expression by E2. Our results indicate that the Stk4 is expressed in Luminal epithelial (LE) and Glandular epithelial (GE) of the uterus and its expression in regulated by the ovarian hormone, Estrogen. These informations will give us on sights to understand uterine dynamics during the estrous cycle.
Regulation of Serine/Threonine Kinase 4 (STK4) expression by estrogen in the mouse uterus
Sohyeon Moon,Sangho Lee,Minha Cho,Boreum Song,Miseon Park,Ok-Hee Lee,Hoon Jang,Youngsok Choi 한국발생생물학회 2017 한국발생생물학회 학술발표대회 Vol.2017 No.8
The Hippo signaling pathway is essential for regulating proliferation, differentiation, and apoptosis in mammalian cells. Hippo signaling pathway exists in most body tissues and organs, where it controls the size of organs and tissues by keeping cell growth in check and promoting cell death as needed. It has been reported that the members of Hippo signaling pathway are highly expressed in mammalian ovaries and uteri. However, the regulatory mechanism of this pathway in the uterus during estrous cycle regulation remains unclear. Serine/Threonine Protein Kinase 4 (STK4, also known as MST1, a homolog of Hippo in Drosophila) is a major factor of Hippo signaling pathway. However STK4 in the mouse uterus has not yet been examined. The purpose of our study was to determine the expression of STK4 during the estrous cycle and regulation by estrogen in the mouse uterus. We found that STK4 was dynamically expressed in uterine endometrium during the estrous cycle. STK4 highly expressed at the estrus, diestrus, and were found to dramatically decrease as it progressed to the proestrus, metestrus stage of uterus during the estrous cycle. Expression of STK4 was dominant in glandular epithelial and luminal epithelial of proestrus, estrus, and diestrus stage, whereas in metestrus stage, expression of gene intensity was faint. Estrogen or estrogen receptor antagonist ICI 182,780 treatment, in ovariectomized mouse uterus, Expression of STK4 and its downstream genes were increased by estrogen. Our results show that the Hippo signaling pathway is estrogen-dependent in the mouse uterus. These informations will give us on sights to understand uterine dynamics during the estrous cycle.
STK3/4 expression is regulated in uterine endometrial dells during the estrous cycle
Sohyeon Moon,Haeun Park,Semi Hwang,Siyoung Lee,Byeongseok Kim,Youngsok Choi 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7
The uterus is dynamically regulated in response to various signaling triggered by hormones during the estrous cycle. The Hippo signaling pathway is known as an important signaling for regulating cellular processes during development by balancing between cell growth and apoptosis. Serine/threonine protein kinase 3/4 (STK3/4) is a key component of the Hippo signaling network. However, the regulation of STK3/4-Hippo signaling in the uterus is little known. In this study, we investigated the regulation and expression of STK3/4 in the uterine endometrium during the estrous cycle. STK3/4 expression was dynamically regulated in the uterus during the estrous cycle. STK3/4protein expression was gradually increased from the diestrus stage and reached the highest in the estrus stage. STK3/4 was exclusively localized in the luminal and glandular epithelial cells of the uterus, and phosphorylated STK3/4 was also increased at the estrus stage. Moreover, the increase of STK3/4 expression in uteri was induced by administration of estradiol, but not by progesterone injection in ovariectomized mice. Pretreatment with an estrogen receptor antagonist ICI 182,780reduced estrogen-induced STK3/4 expression and its phosphorylation. The estrogen-induced STK3/4expression was related to the increase in phosphorylation of downstream targets including LATS1/2and YAP. These findings suggest that STK3/4-Hippo signaling acts a novel signaling pathway in the uterine epithelium and STK3/4-Hippo is one of key molecules for connecting between the estrogen downstream signaling pathway and the Hippo signaling pathway leading to regulate dynamic uterine epithelium during the estrous cycle.