Top

Published in:

Open Access 01-12-2003 | Research

Placental expression of estrogen receptor beta and its hormone binding variant – comparison with estrogen receptor alpha and a role for estrogen receptors in asymmetric division and differentiation of estrogen-dependent cells

Authors: Antonin Bukovsky, Michael R Caudle, Maria Cekanova, Romaine I Fernando, Jay Wimalasena, James S Foster, Donald C Henley, Robert F Elder

Published in: Reproductive Biology and Endocrinology | Issue 1/2003

Abstract

During human pregnancy, the production of 17-beta-estradiol (E2) rises steadily to eighty fold at term, and placenta has been found to specifically bind estrogens. We have recently demonstrated the expression of estrogen receptor alpha (ER-alpha) protein in human placenta and its localization in villous cytotrophoblast (CT), vascular pericytes, and amniotic fibroblasts. In vitro, E2 stimulated development of large syncytiotrophoblast (ST) aggregates. In the present study we utilized ER-beta affinity purified polyclonal (N19:sc6820) and ER-alpha monoclonal (clone h-151) antibodies. Western blot analysis revealed a single ~52 kDa ER-beta band in chorionic villi (CV) protein extracts. In CV, strong cytoplasmic ER-beta immunoreactivity was confined to ST. Dual color immunohistochemistry revealed asymmetric segregation of ER-alpha in dividing villous CT cells. Prior to separation, the cell nuclei more distant from ST exhibited high ER-alpha, while cell nuclei associated with ST showed diminution of ER-alpha and appearance of ER-beta. In trophoblast cultures, development of ST aggregates was associated with diminution of ER-alpha and appearance of ER-beta immunoreactivity. ER-beta was also detected in endothelial cells, amniotic epithelial cells and fibroblasts, extravillous trophoblast (nuclear and cytoplasmic) and decidual cells (cytoplasmic only). In addition, CFK-E12 (E12) and CWK-F12 (F12) monoclonal antibodies, which recognize ~64 kDa ER-beta with hormone binding domain, showed nuclear-specific reactivity with villous ST, extravillous trophoblast, and amniotic epithelium and fibroblasts. Western blot analysis indicated abundant expression of a ~64 kDa ER-beta variant in trophoblast cultures, significantly higher when compared to the chorionic villi and freshly isolated trophoblast cell protein extracts. This is the first report on ER-beta expression in human placenta and cultured trophoblast. Our data indicate that during trophoblast differentiation, the ER-alpha is associated with a less, and ER-beta with the more differentiated state. Enhanced expression of ~64 kDa ER-beta variant in trophoblast cultures suggests a unique role of ER-beta hormone binding domain in the regulation of trophoblast differentiation. Our data also indicate that asymmetric segregation of ER-alpha may play a role in asymmetric division of estrogen-dependent cells.

Available only for authorised users

Diel P: Tissue-specific estrogenic response and molecular mechanisms. Toxicol Lett. 2002, 127: 217-224.CrossRefPubMed

Younes MA, Besch NF, Besch PK: Estradiol and progesterone binding in human term placental cytosol. Am J Obstet Gynecol. 1981, 141: 170-174.PubMed

Kneussl ES, Ances IG, Albrecht ED: A specific cytosolic estrogen receptor in human term placenta. Am J Obstet Gynecol. 1982, 144: 803-809.PubMed

Khan-Dawood FS, Dawood MY: Estrogen and progesterone receptor and hormone levels in human myometrium and placenta in term pregnancy. Am J Obstet Gynecol. 1984, 150: 501-505.CrossRefPubMed

Castracane VD, Goldzieher JW: The relationship of estrogen to placental steroidogenesis in the baboon. J Clin Endocrinol Metab. 1986, 62: 1163-1166.CrossRefPubMed

Baggia S, Albrecht ED, Pepe GJ: Regulation of 11 beta-hydroxysteroid dehydrogenase activity in the baboon placenta by estrogen. Endocrinology. 1990, 126: 2742-2748.CrossRefPubMed

Petraglia F, Vaughan J, Vale W: Steroid hormones modulate the release of immunoreactive gonadotropin-releasing hormone from cultured human placental cells. J Clin Endocrinol Metab. 1990, 70: 1173-1178.CrossRefPubMed

Chibbar R, Wong S, Miller FD, Mitchell BF: Estrogen stimulates oxytocin gene expression in human chorio-decidua. J Clin Endocrinol Metab. 1995, 80: 567-572.PubMed

Shanker YG, Rao AJ: Regulation of progesterone biosynthesis in the human placenta by estradiol 17 beta and progesterone. Biochem Mol Biol Int. 1997, 43: 591-599.PubMed

10.

Sun K, Yang K, Challis JR: Regulation of 11beta-hydroxysteroid dehydrogenase type 2 by progesterone, estrogen, and the cyclic adenosine 5'-monophosphate pathway in cultured human placental and chorionic trophoblasts. Biol Reprod. 1998, 58: 1379-1384.CrossRefPubMed

11.

Pepe GJ, Albrecht ED: Regulation of functional differentiation of the placental villous syncytiotrophoblast by estrogen during primate pregnancy. Steroids. 1999, 64: 624-627.CrossRefPubMed

12.

Taddei G, Noei I, Periti E, Borri P, Torricelli F, Tozzi P, Moncini D, Paglierani M, Branconi F: Chorion villosum does not express progesterone and estrogen receptors during the first trimester of pregnancy. Gynecol Obstet Invest. 1996, 42: 77-79.CrossRefPubMed

13.

Rossmanith WG, Wolfahrt S, Ecker A, Eberhardt E: The demonstration of progesterone, but not of estrogen, receptors in the developing human placenta. Horm Metab Res. 1997, 29: 604-610.CrossRefPubMed

14.

Laminski NA, Hammond KD: Receptors for oestradiol in human placenta. Placenta. 1985, 6: 383-389.CrossRefPubMed

15.

Bukovsky A, Cekanova M, Caudle MR, Wimalasena J, Foster JS, Henley DC, Elder RF: Expression and localization of estrogen receptor-alpha protein in normal and abnormal term placentae and stimulation of trophoblast differentiation by estradiol. Reprod Biol Endocrinol. 2003, 1: 13-PubMedCentralCrossRefPubMed

16.

Rosenfeld CS, Wagner JS, Roberts RM, Lubahn DB: Intraovarian actions of oestrogen. Reproduction. 2001, 122: 215-226.CrossRefPubMed

17.

Girdler F, Brotherick I: The oestrogen receptors (ER alpha and ER beta) and their role in breast cancer: a review. The Breast. 2000, 9: 194-200.CrossRefPubMed

18.

Choi I, Ko C, Park-Sarge OK, Nie R, Hess RA, Graves C, Katzenellenbogen BS: Human estrogen receptor beta-specific monoclonal antibodies: characterization and use in studies of estrogen receptor beta protein expression in reproductive tissues. Mol Cell Endocrinol. 2001, 181: 139-150.CrossRefPubMed

19.

Yang P, Kriatchko A, Roy SK: Expression of ER-alpha and ER-beta in the hamster ovary: differential regulation by gonadotropins and ovarian steroid hormones. Endocrinology. 2002, 143: 2385-2398.PubMed

20.

Gustafsson JA: Estrogen receptor beta – a new dimension in estrogen mechanism of action. J Endocrinol. 1999, 163: 379-383.CrossRefPubMed

21.

Gustafsson JA, Warner M: Estrogen receptor beta in the breast: role in estrogen responsiveness and development of breast cancer. J Steroid Biochem Mol Biol. 2000, 74: 245-248.CrossRefPubMed

22.

Couse JF, Korach KS: Contrasting phenotypes in reproductive tissues of female estrogen receptor null mice. Ann N Y Acad Sci. 2001, 948: 1-8.CrossRefPubMed

23.

Forster C, Makela S, Warri A, Kietz S, Becker D, Hultenby K, Warner M, Gustafsson JA: Involvement of estrogen receptor beta in terminal differentiation of mammary gland epithelium. Proc Natl Acad Sci U S A. 2002, 99: 15578-15583.PubMedCentralCrossRefPubMed

24.

O'Brien ML, Park K, In Y, Park-Sarge OK: Characterization of estrogen receptor-beta (ERbeta) messenger ribonucleic acid and protein expression in rat granulosa cells. Endocrinology. 1999, 140: 4530-4541.CrossRefPubMed

25.

Arnholdt H, Meisel F, Fandrey K, Lohrs U: Proliferation of villous trophoblast of the human placenta in normal and abnormal pregnancies. Virchows Arch B Cell Pathol Incl Mol Pathol. 1991, 60: 365-372.CrossRefPubMed

26.

Esterman A, Greco MA, Mitani Y, Finlay TH, Ismail-Beigi F, Dancis J: The effect of hypoxia on human trophoblast in culture: morphology, glucose transport and metabolism. Placenta. 1997, 18: 129-136.CrossRefPubMed

27.

Yamada Z, Kitagawa M, Takemura T, Hirokawa K: Effect of maternal age on incidences of apoptotic and proliferative cells in trophoblasts of full-term human placenta. Mol Hum Reprod. 2001, 7: 1179-1185.CrossRefPubMed

28.

Shih IM, Kurman RJ: Ki-67 labeling index in the differential diagnosis of exaggerated placental site, placental site trophoblastic tumor, and choriocarcinoma: a double immunohistochemical staining technique using Ki-67 and Mel-CAM antibodies. Hum Pathol. 1998, 29: 27-33.CrossRefPubMed

29.

Jan YN, Jan LY: Asymmetric cell division. Nature. 1998, 392: 775-778.CrossRefPubMed

30.

Shen Q, Temple S: Creating asymmetric cell divisions by skewing endocytosis. Sci STKE. 2002, 2002: E52-

31.

Conboy IM, Rando TA: The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. Dev Cell. 2002, 3: 397-409.CrossRefPubMed

32.

French MB, Koch U, Shaye RE, McGill MA, Dho SE, Guidos CJ, McGlade CJ: Transgenic expression of numb inhibits notch signaling in immature thymocytes but does not alter T cell fate specification. J Immunol. 2002, 168: 3173-3180.CrossRefPubMed

33.

McKenzie JL, Fabre JW: Human Thy-1: unusual localization and possible functional significance in lymphoid tissues. J Immunol. 1981, 126: 843-850.PubMed

34.

Williams AF, Parekh RB, Wing DR, Willis AC, Barclay AN, Dalchau R, Fabre JW, Dwek RA, Rademacher TW: Comparative analysis of the N-glycans of rat, mouse and human Thy-1. Site-specific oligosaccharide patterns of neural Thy-1, a member of the immunoglobulin superfamily. Glycobiology. 1993, 3: 339-348.CrossRefPubMed

35.

Sternberger LA, Joseph SA: The unlabelled antibody method. Contrasting color staining of paired hormones without antibody removal. J Histochem Cytochem. 1979, 27: 1424-1429.CrossRefPubMed

36.

McKenzie PP, Foster JS, House S, Bukovsky A, Caudle MR, Wimalasena J: Expression of G₁ cyclins and cyclin-dependent kinase-2 activity during terminal differentiation of cultured human trophoblast. Biol Reprod. 1998, 58: 1283-1289.CrossRefPubMed

37.

Hayashi H, Ogawa N, Ishiwa N, Yazawa T, Inayama Y, Ito T, Kitamura H: High cyclin E and low p27/Kip1 expressions are potentially poor prognostic factors in lung adenocarcinoma patients. Lung Cancer. 2001, 34: 59-65.CrossRefPubMed

38.

McArthur GA, Foley KP, Fero ML, Walkley CR, Deans AJ, Roberts JM, Eisenman RN: MAD1 and p27(KIP1) cooperate to promote terminal differentiation of granulocytes and to inhibit Myc expression and cyclin E-CDK2 activity. Mol Cell Biol. 2002, 22: 3014-3023.PubMedCentralCrossRefPubMed

39.

Mowa CN, Iwanaga T: Differential distribution of oestrogen receptor-alpha and -beta mRNAs in the female reproductive organ of rats as revealed by in situ hybridization. J Endocrinol. 2000, 165: 59-66.CrossRefPubMed

40.

Wang H, Eriksson H, Sahlin L: Estrogen receptors alpha and beta in the female reproductive tract of the rat during the estrous cycle. Biol Reprod. 2000, 63: 1331-1340.CrossRefPubMed

41.

Pelletier G, El Alfy M: Immunocytochemical localization of estrogen receptors alpha and beta in the human reproductive organs. J Clin Endocrinol Metab. 2000, 85: 4835-4840.PubMed

42.

Jarvinen TA, Pelto-Huikko M, Holli K, Isola J: Estrogen receptor beta is coexpressed with ERalpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer. Am J Pathol. 2000, 156: 29-35.PubMedCentralCrossRefPubMed

43.

Zhou Q, Nie R, Prins GS, Saunders PT, Katzenellenbogen BS, Hess RA: Localization of androgen and estrogen receptors in adult male mouse reproductive tract. J Androl. 2002, 23: 870-881.PubMed

44.

Benirschke K, Kaufmann P: Pathology of the Human Placenta. 1995, New York: Springer, 3CrossRef

45.

Shen Q, Zhong W, Jan YN, Temple S: Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts. Development. 2002, 129: 4843-4853.PubMed

46.

Klotz DM, Hewitt SC, Ciana P, Raviscioni M, Lindzey JK, Foley J, Maggi A, DiAugustine RP, Korach KS: Requirement of estrogen receptor-alpha in insulin-like growth factor-1 (IGF-1)-induced uterine responses and in vivo evidence for IGF-1/estrogen receptor cross-talk. J Biol Chem. 2002, 277: 8531-8537.CrossRefPubMed

47.

Buchanan DL, Kurita T, Taylor JA, Lubahn DB, Cunha GR, Cooke PS: Role of stromal and epithelial estrogen receptors in vaginal epithelial proliferation, stratification, and cornification. Endocrinology. 1998, 139: 4345-4352.PubMed

48.

Kanai M, Shiozawa T, Xin L, Nikaido T, Fujii S: Immunohistochemical detection of sex steroid receptors, cyclins, and cyclin-dependent kinases in the normal and neoplastic squamous epithelia of the uterine cervix. Cancer. 1998, 82: 1709-1719.CrossRefPubMed

49.

Cooke PS, Buchanan DL, Young P, Setiawan T, Brody J, Korach KS, Taylor J, Lubahn DB, Cunha GR: Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium. Proc Natl Acad Sci U S A. 1997, 94: 6535-6540.PubMedCentralCrossRefPubMed

50.

Kraut R, Chia W, Jan LY, Jan YN, Knoblich JA: Role of inscuteable in orienting asymmetric cell divisions in Drosophila. Nature. 1996, 383: 50-55.CrossRefPubMed

51.

Cayouette M, Raff M: Asymmetric segregation of Numb: a mechanism for neural specification from Drosophila to mammals. Nat Neurosci. 2002, 5: 1265-1269.CrossRefPubMed

52.

Petersen PH, Zou K, Hwang JK, Jan YN, Zhong W: Progenitor cell maintenance requires numb and numblike during mouse neurogenesis. Nature. 2002, 419: 929-934.CrossRefPubMed

53.

Kliman HJ, Nestler JE, Sermasi E, Sanger JM, Strauss JF: Purification, characterization, and in vitro differentiation of cytotrophoblasts from human term placentae. Endocrinology. 1986, 118: 1567-1582.CrossRefPubMed

54.

Petraglia F, de Micheroux AA, Florio P, Salvatori M, Gallinelli A, Cela V, Palumbo MA, Genazzani AR: Steroid-protein interaction in human placenta. J Steroid Biochem Mol Biol. 1995, 53: 227-231.CrossRefPubMed

Title: Placental expression of estrogen receptor beta and its hormone binding variant – comparison with estrogen receptor alpha and a role for estrogen receptors in asymmetric division and differentiation of estrogen-dependent cells
Authors: Antonin Bukovsky
Michael R Caudle
Maria Cekanova
Romaine I Fernando
Jay Wimalasena
James S Foster
Donald C Henley
Robert F Elder
Publication date: 01-12-2003
Publisher: BioMed Central
Published in: Reproductive Biology and Endocrinology / Issue 1/2003
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/1477-7827-1-36

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Placental expression of estrogen receptor beta and its hormone binding variant – comparison with estrogen receptor alpha and a role for estrogen receptors in asymmetric division and differentiation of estrogen-dependent cells

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2003

Regulation of intraluteal production of prostaglandins

Recent advancements in corpus luteum development, function, maintenance and regression: Forum introduction

Neural stem cells and the regulation of adult neurogenesis

Signaling mechanisms in tumor necrosis factor alpha-induced death of microvascular endothelial cells of the corpus luteum

The antiestrogen ICI 182,780 decreases the expression of estrogen receptor-alpha but has no effect on estrogen receptor-beta and androgen receptor in rat efferent ductules

The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the mouse