Min Hu1,2, Juan Li1,2, Yuehui Zhang1,3, Xin Li1,4,5, Mats Brännström6, Linus R Shao1, Håkan Billig1. 1. Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg Gothenburg 40530, Sweden. 2. Department of Traditional Chinese Medicine, The First Affiliated Hospital of Guangzhou Medical University Guangzhou 510120, China. 3. Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine Harbin 150040, China. 4. Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200011, China. 5. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011, China. 6. Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Sahlgrenska Academy, University of Gothenburg Gothenburg 41345, Sweden.
Abstract
CONTEXT: Polycystic ovary syndrome (PCOS) affects approximately 4%-18% of all reproductive-aged women and is often accompanied by endometrial progesterone (P4) resistance. Endometrial cells from PCOS patients display increased progesterone receptor (PGR) expression; however, in vivo knockout studies and in vitro experiments indicate the two PGR isoforms are not functionally equivalent. OBJECTIVE: We aimed to compare endometrial PGR isoform expression between non-PCOS and PCOS patients during the proliferative phase. DESIGN: A case-control study. The expression of PGR isoforms (PGRA and PGRB), estrogen receptor alpha (ERα), and markers of cell proliferation was determined by qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence assays. PATIENT(S): Patients were recruited and diagnosed with PCOS according to the Rotterdam criteria provided by the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. Endometrial biopsy samples were collected from non-PCOS patients with regular menstrual cycles or with hyperplasia (n = 11) and from PCOS patients with or without hyperplasia (n = 14). RESULT(S): Although the alteration of PGRB mRNA and protein expression was different, we found that PGRA mRNA and protein expression was higher in PCOS patients than non-PCOS patients. PGRA/B and PGRB were localized in both epithelial and stromal cells, with notable changes in the nuclei of epithelial and stromal cells. A similar expression pattern of ERα, vimentin and Ki-67, in association with an increased PGR expression, was observed in PCOS patients. CONCLUSION(S): These results demonstrated that elevated both PGR isoform expression depends on the presence of PCOS, and our data suggest that abnormal regulation of PGR isoforms is a pathological outcome of defective endometrium in PCOS patients.
CONTEXT: Polycystic ovary syndrome (PCOS) affects approximately 4%-18% of all reproductive-aged women and is often accompanied by endometrial progesterone (P4) resistance. Endometrial cells from PCOSpatients display increased progesterone receptor (PGR) expression; however, in vivo knockout studies and in vitro experiments indicate the two PGR isoforms are not functionally equivalent. OBJECTIVE: We aimed to compare endometrial PGR isoform expression between non-PCOS and PCOSpatients during the proliferative phase. DESIGN: A case-control study. The expression of PGR isoforms (PGRA and PGRB), estrogen receptor alpha (ERα), and markers of cell proliferation was determined by qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence assays. PATIENT(S): Patients were recruited and diagnosed with PCOS according to the Rotterdam criteria provided by the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. Endometrial biopsy samples were collected from non-PCOSpatients with regular menstrual cycles or with hyperplasia (n = 11) and from PCOSpatients with or without hyperplasia (n = 14). RESULT(S): Although the alteration of PGRB mRNA and protein expression was different, we found that PGRA mRNA and protein expression was higher in PCOSpatients than non-PCOSpatients. PGRA/B and PGRB were localized in both epithelial and stromal cells, with notable changes in the nuclei of epithelial and stromal cells. A similar expression pattern of ERα, vimentin and Ki-67, in association with an increased PGR expression, was observed in PCOSpatients. CONCLUSION(S): These results demonstrated that elevated both PGR isoform expression depends on the presence of PCOS, and our data suggest that abnormal regulation of PGR isoforms is a pathological outcome of defective endometrium in PCOSpatients.
Authors: Ricardo Azziz; Enrico Carmina; ZiJiang Chen; Andrea Dunaif; Joop S E Laven; Richard S Legro; Daria Lizneva; Barbara Natterson-Horowtiz; Helena J Teede; Bulent O Yildiz Journal: Nat Rev Dis Primers Date: 2016-08-11 Impact factor: 52.329
Authors: Ricardo F Savaris; Jeremy M Groll; Steven L Young; Franco J DeMayo; Jae-Wook Jeong; Amy E Hamilton; Linda C Giudice; Bruce A Lessey Journal: J Clin Endocrinol Metab Date: 2011-03-16 Impact factor: 5.958