Glucose Transporter Proteins (GLUT) in Human Endometrium: Expression, Regulation, and Function throughout the Menstrual Cycle and in Early Pregnancy

Wolff, Michael von; Ursel, Stefanie; Hahn, Uwe; Steldinger, R.; Strowitzki, T.

doi:10.1210/jc.2002-021890

Cited by 105 publications

(107 citation statements)

References 38 publications

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“…A study of GLUT expression in immature rat uterus only detected the presence of GLUT1 and GLUT4 isoforms (Welch & Gorski 1999), while in the human endometrium only GLUT1 and GLUT3 have been reported (Younes et al 1997, von Wolff et al 2003. In Ishikawa endometrial cancer cells we detected the expression of GLUT1-4 and GLUT6.…”

Section: Discussionmentioning

confidence: 70%

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Differential regulation of glucose transporter expression by estrogen and progesterone in Ishikawa endometrial cancer cells

Medina¹,

Meneses²,

Vera³

et al. 2004

Journal of Endocrinology

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Estrogen replacement therapy and other unopposed estrogen treatments increase the incidence of endometrial abnormalities, including cancer. However, this effect is counteracted by the co-administration of progesterone. In the endometrium, glucose transporter (GLUT) expression and glucose transport are known to fluctuate throughout the menstrual cycle. Here, we determined the effect of estrogen and progesterone on the expression of GLUT1-4 and on the transport of deoxyglucose in Ishikawa endometrial cancer cells. Cells were incubated with estrogen, progesterone or combined estrogen and progesterone for 24 h and the effect on the expression of GLUT1-4 and on deoxyglucose transport was determined. We show that GLUT1 expression is upregulated by estrogen and progesterone individually, but that combined estrogen and progesterone treatment reverses this increase. Hormonal treatments do not affect GLUT2, GLUT3 or GLUT4 expression. Transport studies demonstrate that estrogen increases deoxyglucose transport at Michaelis-Menten constants (K m s) corresponding to GLUT1/4, an effect which disappears when progesterone is added concomitantly. These data demonstrate that different hormonal treatments differentially regulate GLUT expression and glucose transport in this endometrial cancer cell line. This regulation mirrors the role played by estrogen and progesterone on the incidence of cancer in this tissue and suggests that GLUT1 may be utilized by endometrial cancer cells to fuel their demand for increased energy requirement.

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Section: Discussionmentioning

confidence: 70%

“…The normal human endometrium expresses GLUT1 and GLUT3 and the expression of mRNA and protein of these transporters is increased in the secretory phase of the menstrual cycle when estrogen and progesterone levels are high (von Wolff et al 2003). The normal rat uterus expresses GLUT1 and GLUT4.…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of glucose transporter expression by estrogen and progesterone in Ishikawa endometrial cancer cells

Medina¹,

Meneses²,

Vera³

et al. 2004

Journal of Endocrinology

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show abstract

“…Because other GLUTs were demonstrated to have expression in endometrium, [27][28][29][30] and because GLUT8 appeared to be hormonally regulated, 27,30,31 we hypothesized that GLUT1 and GLUT8 would be overexpressed in endometrial cancer compared to benign endometrial tissue, controlled for menopausal status. As with the upregulation of glucose transporters in other cancers, the upregulation of GLUT1 and GLUT8 may identify poorly differentiated, thus more aggressive endometrial tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, von Wolff et al 30 analyzed endometrial tissue for GLUT8 by northern blot analysis and found no GLUT8 mRNA expression. The reason(s) for these differing results is unclear.…”

Section: Discussionmentioning

confidence: 99%

GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma

et al. 2006

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Glucose is provided to cells by a family of glucose transport facilitators known as GLUTs. These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. Regulation of glucose transport facilitator expression has been demonstrated in endometrial tissue and endometrial adenocarcinoma. The following experiments were conducted to quantify and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare this expression to endometrial cancer. Endometrial tissue samples were obtained from random hysterectomy specimens of patients with benign indications for surgery and endometrial cancer. Immunoblot and immunolocatization studies were performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65 women who had undergone hysterectomy were examined (n ¼ 38 benign, n ¼ 27 malignant). A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1 expression was demonstrated with increasing grade of tumors (Po0.002). GLUT8 expression was increased in all tumor subtypes compared to atrophic endometrium (Po0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and endometrial cancer. There appears to be a step-wise progression in GLUT1 and GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be important markers in tumor differentiation, as well as providing energy to rapidly dividing tumor cells.

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“…Insulin gene expression is also influenced by E 2 levels. At proestrus, when estrogen levels peak, insulin mRNA expression is decreased in the pancreas (4), and in the luteal phase of the cycle, the expression of some glucose transporters (GLUTs) in the uterus are also affected (5).…”

Section: Muscle Glut4 Regulation By Estrogen Receptors Er␤ and Er␣mentioning

confidence: 99%

Muscle GLUT4 regulation by estrogen receptors ERβ and ERα

Barros

Machado

Warner

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

236

184

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Estrogen is known to influence glucose homeostasis with dominant effects in the liver, but the role of estrogen receptors in muscle glucose metabolism is unknown. In the present study, we investigated the expression of the two estrogen receptors, ERα and ERβ, and their influence on regulation of the glucose transporter, GLUT4, and its associated structural protein, caveolin-1, in mouse gastrocnemius muscle. Immunohistochemical analysis revealed that ERα and ERβ are coexpressed in the nuclei of most muscle cells, and that their levels were not affected by absence of estradiol [in aromatase-knockout (ArKO) mice]. GLUT4 expression on the muscle cell membrane was not affected by loss of ERβ but was extremely reduced in ERα -/- mice and elevated in ArKO mice. RT-PCR confirmed a parallel reduction in GLUT4 mRNA levels in ERα -/- mice. Upon treatment of ArKO mice with the ERβ agonist 2,3-bis(4-hydroxyphenyl)propionitrile, GLUT4 expression was reduced. By immunofluorescence and Western blotting, caveolin-1 expression was higher in ArKO mice and lower in ERβ -/- and ERα -/- mice than in WT littermates. GLUT4 and caveolin-1 were colocalized in WT and ArKO mice but not in ERβ -/- and ERα -/- mice. These results reveal that ERα is a positive regulator of GLUT4 expression, whereas ERβ has a suppressive role. Both ERβ and ERα are necessary for optimal caveolin-1 expression. Taken together, these results indicate that colocalization of caveolin-1 and GLUT4 is not an absolute requirement for muscle glucose metabolism but that reduction in GLUT4 could be contributing to the insulin resistance observed in ERα -/- mice.

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Glucose Transporter Proteins (GLUT) in Human Endometrium: Expression, Regulation, and Function throughout the Menstrual Cycle and in Early Pregnancy

Cited by 105 publications

References 38 publications

Differential regulation of glucose transporter expression by estrogen and progesterone in Ishikawa endometrial cancer cells

Differential regulation of glucose transporter expression by estrogen and progesterone in Ishikawa endometrial cancer cells

GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma

Muscle GLUT4 regulation by estrogen receptors ERβ and ERα

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