| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Regular Article |
a Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of North Carolina at Chapel Hill, North Carolina 27599
b OB/GYN Clinic, Infertility Department, 60 MSGS/SGCGG, Travis AFB, California 94535-1800
c Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada R3E 3J7
d Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599
Androgen receptors (AR) have been identified in human endometrium; however, their role in endometrial cyclic development and function remains poorly understood. The objective of the present study was to investigate the profile of endometrial AR in normal menstrual cycles and in the endometrium of women with polycystic ovarian syndrome (PCOS). This syndrome is characterized by chronic hyperandrogenism and oligo-ovulation, and it is often associated with poor reproductive performance. Using immunohistochemistry and reverse transcription-polymerase chain reaction, we found that women with PCOS exhibited elevated endometrial AR expression compared to normal, fertile controls. This increase was most apparent in glandular and luminal epithelium. Furthermore, when compared to endometrium from fertile women, PCOS endometrium showed other abnormalities in endometrial development, including delay or absence of the 
vß3 integrin, a well-characterized biomarker of uterine receptivity described previously (Lessey et al., JCI 1992; 90:188–195). To better understand and to gain insights regarding these findings, we used in vitro cell-culture models to study the regulation of AR in primary endometrial stromal and the well-differentiated epithelial cell line (Ishikawa). Based on Western blot analysis, epithelial AR is up-regulated by estrogens and androgens and is inhibited by progestins and epidermal growth factor (EGF). On the other hand, EGF significantly induced the expression of vß3, whereas estrogen and androgen treatment inhibited its expression. Collectively, these results suggest that the poor reproductive performance observed in women with PCOS may be due, in part, to the concomitant increase in both serum androgens and elevations in endometrial AR. This combination may reduce endometrial receptivity as judged by the down-regulation of vß3 integrin.
1 Supported by NICHD/NIH through cooperative agreement U54 HD-35041 (to B.L.) as part of the Specialized Cooperative Centers Program in Reproduction Research, the National Cooperative Program on Markers of Uterine Receptivity for Blastocyst Implantation (HD 34824 to B.L.), the ACOG/Tampbrands Research Fellowship Award (to L.P.L.), and the Fogerty International Fellowship award (to Y.G. and K.B.C.A.R.). Presented at the 33rd Annual Meeting of the Society for the Study of Reproduction in Madison, WI, July 15–18, 2000.
2 Correspondence: Bruce A. Lessey, Department of OB/GYN, CB #7570 Old Clinic Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7570. FAX: 919 966 5214;lessey{at}med.unc.edu
This article has been cited by other articles:
|
|
 |
|
  J. Y. Kim, H. Song, H. Kim, H. J. Kang, J. H. Jun, S. R. Hong, M. K. Koong, and I. S. Kim Transcriptional Profiling with a Pathway-Oriented Analysis Identifies Dysregulated Molecular Phenotypes in the Endometrium of Patients with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1416 - 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. O. D. Critchley and P. T. K. Saunders Hormone Receptor Dynamics in a Receptive Human Endometrium Reproductive Sciences, February 1, 2009; 16(2): 191 - 199. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Palomba, A. Falbo, F. Zullo, and F. Orio Jr. Evidence-Based and Potential Benefits of Metformin in the Polycystic Ovary Syndrome: A Comprehensive Review Endocr. Rev., February 1, 2009; 30(1): 1 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Franks, J. Stark, and K. Hardy Follicle dynamics and anovulation in polycystic ovary syndrome Hum. Reprod. Update, May 22, 2008; (2008) dmn015v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Nagpal, S. Nair, D. Chakravarty, R. Rajhans, S. Pothana, D. W. Brann, R. R. Tekmal, and R. K. Vadlamudi Growth Factor Regulation of Estrogen Receptor Coregulator PELP1 Functions via Protein Kinase A Pathway Mol. Cancer Res., May 1, 2008; 6(5): 851 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Veleva, A. Tiitinen, S. Vilska, C. Hyden-Granskog, C. Tomas, H. Martikainen, and J. S. Tapanainen High and low BMI increase the risk of miscarriage after IVF/ICSI and FET Hum. Reprod., April 1, 2008; 23(4): 878 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bai, G. Grossman, L. Yuan, B. A. Lessey, F. S. French, S. L. Young, and E. M. Wilson Hormone control and expression of androgen receptor coregulator MAGE-11 in human endometrium during the window of receptivity to embryo implantation Mol. Hum. Reprod., February 1, 2008; 14(2): 107 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Horne and D. L. Blithe Progesterone receptor modulators and the endometrium: changes and consequences Hum. Reprod. Update, November 1, 2007; 13(6): 567 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vani, S. E. McDonald, A. R.W. Williams, J. I. Mason, K. J. Thong, and H. O.D. Critchley Mid-luteal endometrial intracrinology following controlled ovarian hyperstimulation involving use of a gonadotrophin releasing hormone antagonist Hum. Reprod., November 1, 2007; 22(11): 2981 - 2991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ishikawa, T. Harada, T. Kubota, and T. Aso Testosterone inhibits matrix metalloproteinase-1 production in human endometrial stromal cells in vitro Reproduction, June 1, 2007; 133(6): 1233 - 1239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rice, K. Ojha, S. Whitehead, and H. Mason Stage-Specific Expression of Androgen Receptor, Follicle-Stimulating Hormone Receptor, and Anti-Mullerian Hormone Type II Receptor in Single, Isolated, Human Preantral Follicles: Relevance to Polycystic Ovaries J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1034 - 1040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Shao, K. Ljungstrom, B. Weijdegard, E. Egecioglu, J. Fernandez-Rodriguez, F.-P. Zhang, A. Thurin-Kjellberg, C. Bergh, and H. Billig Estrogen-induced upregulation of AR expression and enhancement of AR nuclear translocation in mouse fallopian tubes in vivo Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E604 - E614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wen, H. Zhu, S. Murakami, P. C. K. Leung, and C. D. MacCalman Regulation of A Disintegrin And Metalloproteinase with ThromboSpondin Repeats-1 Expression in Human Endometrial Stromal Cells by Gonadal Steroids Involves Progestins, Androgens, and Estrogens J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4825 - 4835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Achache and A. Revel Endometrial receptivity markers, the journey to successful embryo implantation Hum. Reprod. Update, November 1, 2006; 12(6): 731 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. N. Jabbour, R. W. Kelly, H. M. Fraser, and H. O. D. Critchley Endocrine Regulation of Menstruation Endocr. Rev., February 1, 2006; 27(1): 17 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Palomba, T. Russo, F. Orio Jr, A. Falbo, F. Manguso, T. Cascella, A. Tolino, E. Carmina, A. Colao, and F. Zullo Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome Hum. Reprod., February 1, 2006; 21(2): 457 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P Pocar, B Fischer, T Klonisch, and S Hombach-Klonisch Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction Reproduction, April 1, 2005; 129(4): 379 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Vadlamudi, S. Balasenthil, R. R. Broaddus, J.-A. Gustafsson, and R. Kumar Deregulation of Estrogen Receptor Coactivator Proline-, Glutamic Acid-, and Leucine-Rich Protein-1/Modulator of Nongenomic Activity of Estrogen Receptor in Human Endometrial Tumors J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6130 - 6138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Lee, J. M. Song, J. E. Lee, J. H. Park, S. J. Kim, S. M. Kang, J. N. Kwon, M. K. Kim, S. I. Roh, and H. S. Yoon Available human feeder cells for the maintenance of human embryonic stem cells Reproduction, December 1, 2004; 128(6): 727 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Hwang, K.-M. Seow, Y.-H. Lin, L.-W. Huang, B.-C. Hsieh, Y.-L. Tsai, G.-J. Wu, S.-C. Huang, C.-Y. Chen, P.-H. Chen, et al. Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study Hum. Reprod., September 1, 2004; 19(9): 1993 - 2000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bourdeau, J. Deschenes, R. Metivier, Y. Nagai, D. Nguyen, N. Bretschneider, F. Gannon, J. H. White, and S. Mader Genome-Wide Identification of High-Affinity Estrogen Response Elements in Human and Mouse Mol. Endocrinol., June 1, 2004; 18(6): 1411 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Narvekar, S. Cameron, H. O. D. Critchley, S. Lin, L. Cheng, and D. T. Baird Low-Dose Mifepristone Inhibits Endometrial Proliferation and Up-Regulates Androgen Receptor J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2491 - 2497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Lessey Endometrial Responsiveness to Steroid Hormones: A Moving Target Reproductive Sciences, February 1, 2004; 11(2): 61 - 62. [PDF]
|
|
|
|
 |
|
 H. Cardenas and W. F. Pope Attenuation of Estrogenic Effects by Dihydrotestosterone in the Pig Uterus Is Associated with Downregulation of the Estrogen Receptors Biol Reprod, February 1, 2004; 70(2): 297 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Burton, T. A. Henderson, S. G. Hillier, J.I. Mason, F. Habib, R. M. Brenner, and H. O.D. Critchley Local levonorgestrel regulation of androgen receptor and 17{beta}-hydroxysteroid dehydrogenase type 2 expression in human endometrium Hum. Reprod., December 1, 2003; 18(12): 2610 - 2617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Brenner, O. D. Slayden, W. H. Rodgers, H. O.D. Critchley, R. Carroll, X. J. Nie, and K. Mah Immunocytochemical assessment of mitotic activity with an antibody to phosphorylated histone H3 in the macaque and human endometrium Hum. Reprod., June 1, 2003; 18(6): 1185 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. W. Gregory, E. M. Wilson, K. B. C. Apparao, R. A. Lininger, W. R. Meyer, A. Kowalik, M. A. Fritz, and B. A. Lessey Steroid Receptor Coactivator Expression throughout the Menstrual Cycle in Normal and Abnormal Endometrium J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2960 - 2966. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
