Lack of cyclical fluctuations of endometrial GLUT4 expression in women with polycystic ovary syndrome: Evidence for direct regulation of GLUT4 by steroid hormones

Peng Cui; Xin Li; Xiaoqin Wang; Yi Feng; Jin-Fang Lin; Håkan Billig; Ruijin Shao

doi:10.1016/j.bbacli.2015.08.004

Lack of cyclical fluctuations of endometrial GLUT4 expression in women with polycystic ovary syndrome: Evidence for direct regulation of GLUT4 by steroid hormones

BBA Clin. 2015 Aug 28:4:85-91. doi: 10.1016/j.bbacli.2015.08.004. eCollection 2015 Dec.

Authors

Peng Cui¹, Xin Li², Xiaoqin Wang³, Yi Feng⁴, Jin-Fang Lin⁵, Håkan Billig⁶, Ruijin Shao⁶

Affiliations

¹ Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Shanghai Medical College and Institute of Acupuncture Research (WHO Collaborating Center for Traditional Medicine), Institute of Brain Science, Fudan University, 200032 Shanghai, China.
² Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden ; Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 200011, Shanghai China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 200011 Shanghai, China.
³ Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg 40530, Sweden.
⁴ Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Shanghai Medical College and Institute of Acupuncture Research (WHO Collaborating Center for Traditional Medicine), Institute of Brain Science, Fudan University, 200032 Shanghai, China ; Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
⁵ Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 200011, Shanghai China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 200011 Shanghai, China.
⁶ Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.

Abstract

Background Determination of the role of steroid hormones in expression and regulation of endometrial glucose transport 4 (GLUT4) in humans is important for understanding endometrial disorders such as polycystic ovary syndrome (PCOS), a common hormone-imbalance disease. Methods Endometrial biopsy samples were collected from non-PCOS patients with regular menstrual cycles or with hyperplasia and from PCOS patients with or without hyperplasia. In addition, endometrial tissues from postmenopausal women were incubated with human chorionic gonadotropin (hCG, 10 IU/ml), 17β-estradiol (E2, 10 nM), progesterone (P4, 100 nM), or a combination of E2 and P4 for 24 h. The expression of GLUT4 was measured at the mRNA level using quantitative real-time polymerase chain reaction (qRT-PCR) and at the protein level using Western blot analysis and immunohistochemistry. Results A cyclical change in GLUT4 expression pattern was observed in non-PCOS patients, and a high level of GLUT4 expression was seen in the proliferative phase compared to the secretory phase. Low levels of GLUT4 expression were found in PCOS patients compared to menstrual cycle phase-matched non-PCOS patients, and there was no significant change in GLUT4 expression in PCOS patients during the menstrual cycle. GLUT4 was localized in both epithelial and stromal cells, with notable changes in epithelial cells. We postulate that decreased GLUT4 expression might be regulated by steroid hormones. In support of this, we showed that in cultured endometrial tissues hCG and E2 alone had no effect on GLUT4 expression. However, P4 alone and P4 in combination with E2 decreased GLUT4 expression. Compared with non-PCOS controls, PCOS patients with endometrial hyperplasia exhibited decreased GLUT4 expression in particular in the epithelial cells. Conclusion We conclude that P4 can induce changes in endometrial GLUT4 expression during the menstrual cycle and that abnormal hormonal conditions such as PCOS disrupt normal patterns of GLUT4 expression in endometrial cells.

Keywords: Endometrium; Glucose transport 4; Menstrual cycle; PCOS; Steroid hormones.