The effects of estrogen, its antagonist ICI 182, 780, and interferon-tau on the expression of estrogen receptors and integrin alphaV beta 3 on cycle day 16 in bovine endometrium

Reproductive Biology and Endocrinology

Leslie A MacLaren²  Brian K Hall¹  Hai Choo Lim²  Gerald L Russell²  Sarah Kimmins² 

[1] Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada;Department of Plant and Animal Sciences, Nova Scotia Agricultural College, Truro, Nova Scotia, Canada

关键词: Steroid Receptors;    Cell Adhesion Molecules;    Hormone Antagonists;    Estrogens;    Endometrium;   

Others  :  1156955
DOI  :  10.1186/1477-7827-1-38

 received in 2003-02-05, accepted in 2003-04-24,  发布年份 2003

【 摘 要 】

We have shown previously that downregulation of intercaruncular stromal integrin α_vβ₃ in bovine endometrium on day 16 of the estrous cycle coincided with the antibody recognition of estrogen receptors (ER) in the luminal epithelium. In pregnancy, these changes were not observed. Our hypothesis was that on day 16 of the estrous cycle, estrogen from the dominant follicle causes a reduction in integrin α_vβ₃ and affects ERα in the luminal epithelium. The pregnancy recognition protein, interferon-τ (IFN-τ), may prevent downregulation of integrin α_vβ₃ and suppress ERα expression in the luminal epithelium. On days 14 to 16, heifers received uterine infusions of the anti-estrogen ICI 182, 780, estradiol 17β, IFN-τ or the saline control. On day 16, reproductive tracts were collected for analysis of integrin α_vβ₃ and ERα. Estrogen receptor α immunoreactivity was largely restricted to the luminal epithelium in control animals. Using anti-ERα recognizing the amino terminus, estrogen-treated animals showed reactivity in the stroma, shallow and deep glands and myometrium as is typical of estrus, whereas ICI 182, 870 treated heifers showed little or no reactivity. In contrast, carboxyl terminus-directed antibodies showed a widespread distribution of ERα with reactivity detected in the uterine epithelium, stroma and myometrium of both estrogen and ICI 182, 780 treated animals. Heifers treated with IFN-τ had low ERα reactivity overall. Control and IFN-τ treated heifers had lower intercaruncular stromal expression of integrin α_vβ₃ in comparison to estrogen and ICI 182, 780 treatments. Overall, the results suggest that on day 16 of the estrous cycle, estrogen effects on integrin α_vβ₃ are indirect and do not directly involve ERα in the luminal epithelium. During pregnancy, interferon-tau may block ERα in the luminal epithelium but likely does not rescue integrin α_vβ₃ expression.

【 授权许可】

   
2003 Kimmins et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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【 参考文献 】

• [1]Betteridge KJ, Eaglesome MD, Randall GC, Mitchell D: Collection, description and transfer of embryos from cattle 10–16 days after oestrus. J Reprod Fertil 1980, 59:205-16.
• [2]McCracken JA, Custer EE, Lamsa JC: Luteolysis: a neuroendocrine-mediated event. Physiol Rev 1999, 79:263-323.
• [3]Kimmins S, MacLaren LA: Cyclic modulation of integrin expression in bovine endometrium. Biol Reprod 1999, 61:1267-74.
• [4]Kimmins S, MacLaren LA: Oestrous cycle and pregnancy effects on the distribution of oestrogen and progesterone receptors in bovine endometrium. Placenta 2001, 22:742-8.
• [5]Hynes RO: Integrins: Bidirectional, allosteric signalling machines. Cell 2002, 110:673-687.
• [6]Lessey BA, Ilrsanmi AO, Lessey MA, Riben M, Harris JE, Chwalisz K: Luminal and glandular endometrial epithelium express integrins differentially throughout the menstrual cycle: implications for implantation, contraception and infertility. Am J Reprod Immunol 1996, 5:3195-204.
• [7]Bowen JA, Bazer FW, Burghardt RC: Spatial and temporal analyses of integrin and Muc-1 expression in porcine uterine epithelium and trophectoderm in vitro. Biol Reprod 1997, 56:409-15.
• [8]Fazleabas AT, Bell SC, Fleming S, Sun J, Lessey BA: Distribution of integrins and the extracellular matrix proteins in the baboon endometrium during the menstrual cycle and early pregnancy. Biol Reprod 1997, 56:348-56.
• [9]Johnson GA, Bazer FW, Jaeger LA, Ka H, Garlow JE, Pfarrer C, Spencer TE, Burghardt RC: Muc-1, integrin, and osteopontin expression during the implantation cascade in sheep. Biol Reprod 2001, 65:820-8.
• [10]Kimmins S, Lim HC, MacLaren LA: Differential Expression of the integrin avβ3 in caruncular and intercaruncular bovine endometrium. Theriogenology 1999, 51:227.
• [11]Li CF, Ross FP, Cao X, Teitelbaum SL: Estrogen enhances alpha v beta 3 integrin expression by avian osteoclast precursors via stabilization of beta 3 integrin mRNA. Mol Endocrinol 1995, 9:805-13.
• [12]Somkuti SG, Yuan L, Fritz MA, Lessey BA: Epidermal growth factor and sex steroids dynamically regulate a marker of endometrial receptivity in Ishikawa cells. J Clin Endocrinol Metab 1997, 82:2192-97.
• [13]Kimmins S, Lim HC, Parent J, Fortier MA, MacLaren LA: The effects of estrogen and progesterone on prostaglandins and integrin beta 3 (β3) subunit expression in primary cultures of bovine endometrial cells. Domest Anim Endocrinol 2003, in press.
• [14]Ivell R, Walther N: The role of sex steroids in the oxytocin hormone system. Mol Cell Endocrinol 1999, 151:95-101.
• [15]Thatcher WW, Terqui M, Thimonier J, Mauleon P: Effect of estradiol-17 beta on peripheral plasma concentration of 15-keto-13,14-dihydro PGF2 alpha and luteolysis in cyclic cattle. Prostaglandins 1986, 31:745-56.
• [16]Salfen BE, Cresswell JR, Xu ZZ, Bao B, Garverick HA: Effects of the presence of a dominant follicle and exogenous oestradiol on the duration of the luteal phase of the bovine oestrous cycle. J Reprod Fertil 1999, 115:15-21.
• [17]Spencer TE, Bazer FW: Temporal and spatial alterations in uterine estrogen receptor and progesterone receptor gene expression during the estrous cycle and early pregnancy in the ewe. Biol Reprod 1995, 53:1527-43.
• [18]Spencer TE, Becker WC, George P, Mirando MA, Ogle TF, Bazer FW: Ovine interferon-tau inhibits estrogen receptor up-regulation and estrogen-induced luteolysis in cyclic ewes. Endocrinology 1995, 136:4932-44.
• [19]Spencer TE, Bazer FW: Ovine interferon tau suppresses transcription of the estrogen receptor and oxytocin receptor genes in ovine endometrium. Endocrinology 1996, 137:1144-47.
• [20]Robinson RS, Mann GE, Lamming GE, Wathes DC: Expression of oxytocin, oestrogen and progesterone receptors in uterine biopsy samples throughout the oestrous cycle and early pregnancy in cows. Reproduction 2001, 122:965-79.
• [21]Schuler G, Wirth C, Teichmann U, Failing K, Leiser R, Thole H, Hoffmann B: Occurrence of estrogen receptor alpha in bovine placentomes throughout mid and late gestation and at parturition. Biol Reprod 2002, 66:976-82.
• [22]MacGregor JI, Jordan VC: Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev 1998, 50:151-96.
• [23]Wakeling AE: Similarities and distinctions in the mode of action of different classes of antioestrogens. Endocr Relat Cancer 2000, 7:17-28.
• [24]Tarleton BJ, Wiley AA, Bartol FF: Endometrial development and adenogenesis in the neonatal pig: effects of estradiol valerate and the antiestrogen ICI 182,780. Biol Reprod 1999, 61:253-63.
• [25]Ford SP, Chenault JR: Blood flow to the corpus luteum-bearing ovary and ipsilateral uterine horn of cows during the oestrous cycle and early pregnancy. J Reprod Fertil 1981, 62:555-62.
• [26]Robertson JA, Zhang Y, Ing NH: ICI 182,780 acts as a partial agonist and antagonist of estradiol effects in specific cells of the sheep uterus. J Steroid Biochem Mol Biol 2001, 77:281-7.
• [27]Meyer MD, Hansen PJ, Thatcher WW, Drost M, Badinga L, Roberts RM, Li J, Ott TL, Bazer FW: Extension of corpus luteum lifespan and reduction of uterine secretion of prostaglandin F2 alpha of cows in response to recombinant interferon-tau. J Dairy Sci 1995, 78:1921-31.
• [28]Ireland A: Follicular development during the four stages of the estrous cycle of beef cattle. J Anim Sci 1979, 49:1261-1264.
• [29]Neff S, Mason PW, Baxt B: High efficiency utilization of the bovine integrin αvβ3 as a receptor for foot and mouth disease virus is dependent on the bovine β3 subunit. J Virol 2000, 74:7298-7306.
• [30]Boos A, Meyer W, Schwarz R, Grunert E: Immunohistochemical assessment of estrogen receptor and progesterone receptor distribution in biopsy samples of the bovine endometrium collected throughout the estrous cycle. Anim Reprod Sci 1996, 44:11-21.
• [31]Leung ST, Wathes DC: Oestradiol regulation of oxytocin receptor expression in cyclic bovine endometrium. J Reprod Fertil 2000, 119:287-92.
• [32]Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, et al.: Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 1995, 270:1491-4.
• [33]Nephew KP, Ray S, Hlaing M, Ahluwalia A, Wu SD, Long X, Hyder SM, Bigsby RM: Expression of estrogen receptor coactivators in the rat uterus. Biol Reprod 2000, 63:361-67.
• [34]Bartol FF, Wiley AA, Floyd JG, Ott TL, Bazer FW, Gray CA, Spencer TE: Uterine differentiation as a foundation for subsequent fertility. J Reprod Fertil 1999, 54:287-02.
• [35]Spencer TE, Ott TL, Bazer FW: Expression of interferon regulatory factors one and two in the ovine endometrium: effects of pregnancy and ovine interferon tau. Biol Reprod 1998, 58:1154-62.
• [36]Fleming JA, Choi Y, Johnson GA, Spencer TE, Bazer FW: Cloning of the ovine estrogen receptor-alpha promoter and functional regulation by ovine interferon-tau. Endocrinology 2001, 142:2879-87.
• [37]Robinson RS, Mann GE, Lamming GE, Wathes DC: The effect of pregnancy on the expression of uterine oxytocin, oestrogen and progesterone receptors during early pregnancy in the cow. J Endocrinol 1999, 160:21-33.
• [38]McHugh KP, Kitazawa S, Teitelbaum SL, Ross FP: Cloning and characterization of the murine beta(3) integrin gene promoter: identification of an interleukin-4 responsive element and regulation by STAT-6. J Cell Biochem 2001, 81:320-32.
• [39]Wilhide CC, Jin Y, Guo Q, Li L, Li SX, Rubin E, Bray PF: The human integrin beta3 gene is 63 kb and contains a 5'-UTR sequence regulating expression. Blood 1997, 90:3951-61.
• [40]Qin C, Singh P, Safe S: Transcriptional activation of insulin-like growth factor-binding protein-4 by 17beta-estradiol in MCF-7 cells: role of estrogen receptor-Sp1 complexes. Endocrinology 1999, 140:2501-8.
• [41]Vyhlidal C, Samudio I, Kladde MP, Safe S: Transcriptional activation of transforming growth factor alpha by estradiol: requirement for both a GC-rich site and an estrogen response element half-site. J Mol Endocrinol 2000, 24:329-38.
• [42]Klinge CM: Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res 2001, 29:2905-19.
• [43]Taylor HS, Arici A, Olive D, Igarashi P: HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest 1998, 101:1379-84.
• [44]Daftary GS, Troy PJ, Bagot CN, Young SL, Taylor HS: Direct regulation of beta3-integrin subunit gene expression by HOXA10 in endometrial cells. Mol Endocrinol 2002, 16:571-9.
• [45]Kurita T, Lee KJ, Cooke PS, Lydon JP, Cunha GR: Paracrine regulation of epithelial progesterone receptor and lactoferrin by progesterone in the mouse uterus. Biol Reprod 2000, 62:831-8.
• [46]Martal J, Chene N, Camous S, Huynh L, Lantier F, Hermier P, L'Haridon R, Charpigny G, Charlier M, Chaouat G: Recent developments and potentialities for reducing embryo mortality in ruminants: the role of IFN-tau and other cytokines in early pregnancy. Reprod Fertil Dev 1997, 9:355-80.
• [47]Choi Y, Johnson GA, Burghardt RC, Berghman LR, Joyce MM, Taylor KM, Stewart MD, Bazer FW, Spencer TE: Interferon regulatory factor-two restricts expression of interferon-stimulated genes to the endometrial stroma and glandular epithelium of the ovine uterus. Biol Reprod 2001, 65:1038-49.