Expression of estrogen and progesterone receptor genes in endometrium, myometrium and vagina of postmenopausal women treated with estriol
Keywords:
Receptors, estrogen, Receptors, progesterone, Estriol, Hormone replacement therapy, Reverse transcriptase polymerase chain reactionAbstract
CONTEXT AND OBJECTIVE: Estriol is an estrogen with considerably weaker stimulatory effects on endometrial proliferation than estradiol. A study was conducted to determine the level of estrogen receptors (ERs) and progesterone receptors (PRs) in women who received 14-day vaginal estriol therapy, compared with those who did not receive this therapy. ER and PR gene expression was analyzed in the endometrium, myometrium and vagina of postmenopausal women treated with estriol. DESIGN AND SETTING: Analytical cross-sectional study, at the Research Institute of the Polish Mothers’ Memorial Hospital, Lodz, Poland. METHODS: Twenty-seven postmenopausal women (57-74 years of age) were included in the study. All of them were waiting for per vaginam hysterectomy or plastic surgery on the vagina and perineum because of uterine prolapse. ER and PR gene expression was determined by means of the technique of reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In the estriol-treated patients, in comparison with the control group, a significant increase in ER gene expression was observed in the endometrium and vagina, while enhanced PR gene expression was found in the endometrium. However, under histological examination of the endometrium, estrogen stimulation of low and medium degree was diagnosed for 21.4% and 14.3% of the estriol-treated women, respectively. CONCLUSION: The results obtained suggest that the women who received 14 days of treatment with vaginal estriol had higher ER and PR mRNA levels. No difference between these groups regarding endometrial proliferation was observed.
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World Health Organization. Research on the menopause in the 1990s. Report of a WHO Scientific Group. Technical Report Series, No 866. Geneva: World Health Organization; 1996.
Rich RL, Hoth LR, Geoghegan KF, et al. Kinetic analysis of estrogen receptor/ligand interac- tions. Proc Natl Acad Sci U S A. 2002;99(13):8562-7.
Peck JD, Hulka BS, Poole C, Savitz DA, Baird D, Richardson BE. Steroid hormone levels during pregnancy and incidence of maternal breast cancer. Cancer Epidemiol Biomarkers Prev. 2002;11(4):361-8.
Fujimoto J, Sakaguchi H, Aoki I, Toyoki H, Tamaya T. Clinical implications of the expression of estrogen receptor-alpha and -beta in primary and metastatic lesions of uterine endometrial cancers. Oncology. 2002;62(3):269-77.
Ito K, Utsunomiya H, Yaegashi N, Sasano H. Biological roles of estrogen and progesterone in human endometrial carcinoma—new developments in potential endocrine therapy for endometrial cancer. Endocr J. 2007;54(5):667-79.
Hanstein B, Beckmann MW, Bender HG. Charakterisierung und Bedeutung verschiedener Ostrogenrezeptortypen unter besonderer Berücksichtigung des Endometriumkarzinoms [Role of estrogen receptor isoforms in the pathogenesis and treatment of endometrial can- cer]. Zentralbl Gynakol. 2002;124(1):17-9.
Jazaeri AA, Nunes KJ, Dalton MS, Xu M, Shupnik MA, Rice LW. Well-differentiated endometrial adenocarcinomas and poorly differentiated mixed mullerian tumors have altered ER and PR isoform expression. Oncogene. 2001;20(47):6965-9.
Gräser T, Koytchev R, Müller A, Oettel M. Comparison of the efficacy and endometrial safety of two estradiol valerate/dienogest combinations and Kliogest for continuous combined hor- mone replacement therapy in postmenopausal women. Climacteric. 2000;3(2):109-18.
Kajta M, Budziszewska B, Marszal M, Lason W. Effects of 17-beta estradiol and estriol on NMDA-induced toxicity and apoptosis in primary cultures of rat cortical neurons. J Physiol Pharmacol. 2001;52(3):437-46.
Parker MG, Arbuckle N, Dauvois S, Danielian P, White R. Structure and function of the estro- gen receptor. Ann N Y Acad Sci. 1993;684:119-26.
Le Marchand L, Donlon T, Kolonel LN, Henderson BE, Wilkens LR. Estrogen metabolism- related genes and breast cancer risk: the multiethnic cohort study. Cancer Epidemiol Bio- markers Prev. 2005;14(8):1998-2003.
Yu J, Yu J, Cordero KE, et al. A transcriptional fingerprint of estrogen in human breast cancer predicts patient survival. Neoplasia. 2008;10(1):79-88.
Klein-Hitpass L, Schwerk C, Kahmann S, Vassen L. Targets of activated steroid hormo- ne receptors: basal transcription factors and receptor interacting proteins. J Mol Med. 1998;76(7):490-6.
Kano H, Hayashi T, Sumi D, et al. Estriol retards and stabilizes atherosclerosis through an NO-mediated system. Life Sci. 2002;71(1):31-42.
Taylor M. Unconventional estrogens: estriol, biest, and triest. Clin Obstet Gynecol. 2001;44(4):864-79.
Teede HJ, Liang YL, Kotsopoulos D, Zoungas S, Cravent R, McGrath BP. A placebo-controlled trial of long-term oral combined continuous hormone replacement therapy in postmeno- pausal women: effects on arterial compliance and endothelial function. Clin Endocrinol (Oxf). 2001;55(5):673-82.
Pardini D. Terapia hormonal da menopausa [Menopausal hormone therapy]. Arq Bras Endo- crinol Metabol. 2007;51(6):938-42.
Estevão RA, Baracat EC, Logullo AF, Oshima CT, Nazário AC. Efficacy of estriol in inhibiting epithelial proliferation in mammary fibroadenoma: randomized clinical trial. Sao Paulo Med J. 2007;125(6):343-50.
Estevão RA, Nazário AC, Baracat EC. Effect of oral contraceptive with and without associated estriol on ultrasound measurements of breast fibroadenoma: randomized clinical trial. Sao Paulo Med J. 2007;125(5):275-80.
Henriksson L, Stjernquist M, Boquist L, Alander U, Selinus I. A comparative multicenter study of the effects of continuous low-dose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and signs of urogenital atrophy. Am J Obstet Gynecol. 1994;171(3):624-32.
van Haaften M, Donker GH, Sie-Go DM, Haspels AA, Thijssen JH. Biochemical and histolo- gical effects of vaginal estriol and estradiol applications on the endometrium, myometrium and vagina of postmenopausal women. Gynecol Endocrinol. 1997;11(3):175-85.
Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocya- nate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156-9.
Chevillard S, Müller A, Levalois C, Lainé-Bidron C, Vielh P, Magdelénat H. Reverse transcrip- tion-polymerase chain reaction (RT-PCR) assays of estrogen and progesterone receptors in breast cancer. Breast Cancer Res Treat. 1996;41(1):81-9.
Bassam BJ, Caetano-Anollés G, Gresshoff PM. Fast and sensitive silver staining of DNA in polyacrylamide gels. Anal Biochem. 1991;196(1):80-3.
Latchman DS. Eukaryotic transcription factors. 2nd ed. London: Academic Press; 1995.
Latchman DS. Transcription factors: an overview. Int J Biochem Cell Biol. 1997;29(12): 1305-12.
McDonnell DP, Clemm DL, Hermann T, Goldman ME, Pike JW. Analysis of estrogen re- ceptor function in vitro reveals three distinct classes of antiestrogens. Mol Endocrinol. 1995;9(6):659-69.
McDonnell DP, Clemm DL, Imhof MO. Definition of the cellular mechanisms which distin- guish between hormone and antihormone activated steroid receptors. Semin Cancer Biol. 1994;5(5):327-36.
Pardini D. Terapêutica de reposição hormonal na osteoporose da pós-menopausa [Hormo- nal replacement therapy in osteoporosis of postmenopausal]. Arq Bras Endocrinol Metab. 1999;43(6):428-32.
Tzukerman MT, Esty A, Santiso-Mere D, et al. Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functio- nally distinct intramolecular regions. Mol Endocrinol. 1994;8(1):21-30.
Webb P, Lopez GN, Uht RM, Kushner PJ. Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens. Mol En- docrinol. 1995;9(4):443-56.
Graham JD, Clarke CL. Physiological action of progesterone in target tissues. Endocr Rev. 1997;18(4):502-19.
Wlaźlak E, Surkont G, Suzin J. Estradiol – nowość czy standard w terapii dopochwowej. Przegląd Menopauzalny. 2004;5(2):50-6. Available from: http://www.termedia.pl/maga- zine.php?magazine_id=4&article_id=2640&magazine_subpage=ABSTRACT. Accessed in 2009 (Jun 15).
Kumar MV, Tindall DJ. Transcriptional regulation of the steroid receptor genes. Prog Nucleic Acid Res Mol Biol. 1998;59:289-306.
Gerbaldo D, Ferraiolo A, Croce S, Truini M, Capitanio GL. Endometrial morphology after 12 months of vaginal oestriol therapy in post-menopausal women. Maturitas. 1991;13(4): 269-74.
Ciszko B, Zdrojewicz Z. Znaczenie endogennego i egzogennego estriolu w praktyce klini- cznej [Compliance endogenous and exogenous estriol in clinical practice]. Ginekol Pol. 2006;77(7):559-65.
Englund DE, Johansson ED. Endometrial effect of oral estriol treatment in postmenopausal women. Acta Obstet Gynecol Scand. 1980;59(5):449-51.
Van Gorp T, Neven P. Endometrial safety of hormone replacement therapy: review of literatu- re. Maturitas. 2002;42(2):93-104.
Weiderpass E, Baron JA, Adami HO, et al. Low-potency oestrogen and risk of endometrial cancer: a case-control study. Lancet. 1999;353(9167):1824-8.
