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PMID: 10537162 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Differential uterine expression of estrogen and progesterone receptors correlates with uterine preparation for implantation and decidualization in the mouse.

Endocrinology ·Vol. 140 ·No. 11 ·1999-11-00 ·Pages 5310-21

Tan J, Paria BC, Dey SK, Das SK

Abstract

The present investigation examined the spatiotemporal expression of estrogen receptors (ER-alpha and ER-beta) and progesterone receptor (PR) in the periimplantation mouse uterus (days 1-8). ER-alpha messenger RNA (mRNA) was detected at much higher levels in the periimplantation uterus compared with that of ER-beta mRNA, the levels of which were very low in all uterine cells during this period. Results of in situ hybridization demonstrated expression of ER-alpha mRNA primarily in the luminal and glandular epithelia on days 1 and 2 of pregnancy. On days 3 and 4, the accumulation was localized primarily in stromal cells in addition to its presence in the epithelium. Following implantation on day 5, the accumulation of this mRNA was more condensed in the luminal and glandular epithelia, but declined in the subluminal epithelial stroma at the sites of implanting embryos. On days 6-8, the accumulation of ER-alpha mRNA was primarily localized in the secondary decidual zone (SDZ) with more intense localization in the subepithelial cells at the mesometrial pole. In contrast, signals were very low to undetectable in the primary decidual zone (PDZ), and no signals were detected in implanting embryos. The undifferentiated stroma underneath the myometrium also showed positive signals. The immunolocalization of ER-alpha protein correlated with the mRNA localization. Western blot analysis showed down-regulation of ER-alpha in day 8 decidual cell extracts consistent with the down-regulation of ER-alpha mRNA in decidual cells immediately surrounding the embryo on this day. The expression pattern of PR was also dynamic in the periimplantation uterus. On day 1, the accumulation of PR mRNA was very low to undetectable, whereas only a modest level of accumulation in the epithelium was noted on day 2. On days 3 and 4, the accumulation of this mRNA was detected in both the epithelium and stroma. In contrast, the expression was restricted only to the stroma with increased signals at the sites of implantation on day 5. On days 6-8, PR mRNA accumulation increased dramatically throughout the deciduum. The localization of immunoreactive PR correlated with the mRNA distribution in the periimplantation uterus. Taken together, the results demonstrate that the expression of ER-alpha, ER-beta, and PR is differentially regulated in the periimplantation mouse uterus. This compartmentalized expression of ER and PR provides information regarding the sites of coordinated effects ofestrogen and progesterone in the preparation of the uterus for implantation and decidualization during early pregnancy.

MeSH Terms
Animals Blotting, Northern Blotting, Western Decidua/physiology Embryo Implantation Female Gene Expression In Situ Hybridization Mice Pregnancy RNA, Messenger/analysis Receptors, Estrogen/genetics Receptors, Progesterone/genetics Uterus/chemistry,physiology
Chemicals
RNA, Messenger Receptors, Estrogen Receptors, Progesterone
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Tan J
Department of Obstetrics & Gynecology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City 66160-7338, USA.
Paria B C
Dey S K
Das S K
References (62)
62 references, click to expand
  1. Hypertrophy and hyperplasia in the mouse uterus after oestrogen treatment: an autoradiographic study.
    J Endocrinol. 1973 Jan;56(1):133-44 PMID: 4683406
  2. Differential spatiotemporal regulation of lactoferrin and progesterone receptor genes in the mouse uterus by primary estrogen, catechol estrogen, and xenoestrogen.
    Endocrinology. 1998 Jun;139(6):2905-15 PMID: 9607801
  3. The steroid and thyroid hormone receptor superfamily.
    Science. 1988 May 13;240(4854):889-95 PMID: 3283939
  4. Expression of transforming growth factor-beta isoforms (beta 2 and beta 3) in the mouse uterus: analysis of the periimplantation period and effects of ovarian steroids.
    Endocrinology. 1992 Jun;130(6):3459-66 PMID: 1375903
  5. Uterine decidual response occurs in estrogen receptor-alpha-deficient mice.
    Endocrinology. 1999 Jun;140(6):2704-10 PMID: 10342861
  6. Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse.
    Endocrinology. 1997 Nov;138(11):4613-21 PMID: 9348186
  7. Differential regulation of heparin-binding epidermal growth factor-like growth factor in the adult ovariectomized mouse uterus by progesterone and estrogen.
    Endocrinology. 1994 Sep;135(3):1264-71 PMID: 8070372
  8. Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta.
    Mol Endocrinol. 1997 Mar;11(3):353-65 PMID: 9058381
  9. Antagonist-occupied human progesterone B-receptors activate transcription without binding to progesterone response elements and are dominantly inhibited by A-receptors.
    Mol Endocrinol. 1993 Oct;7(10):1256-65 PMID: 8123133
  10. Cell type-specific localization of c-myc protein in the mouse uterus: modulation by steroid hormones and analysis of the periimplantation period.
    Endocrinology. 1989 Sep;125(3):1683-90 PMID: 2667965
  11. Mouse estrogen receptor beta forms estrogen response element-binding heterodimers with estrogen receptor alpha.
    Mol Endocrinol. 1997 Sep;11(10):1486-96 PMID: 9280064
  12. Differential immunolocalization of estrogen receptor alpha and beta in rat ovary and uterus.
    J Mol Endocrinol. 1999 Feb;22(1):37-44 PMID: 9924178
  13. Lactoferrin in the mouse uterus: analyses of the preimplantation period and regulation by ovarian steroids.
    Mol Endocrinol. 1992 Jan;6(1):101-11 PMID: 1738363
  14. Stromal progesterone receptors mediate the inhibitory effects of progesterone on estrogen-induced uterine epithelial cell deoxyribonucleic acid synthesis.
    Endocrinology. 1998 Nov;139(11):4708-13 PMID: 9794483
  15. Amphiregulin is an implantation-specific and progesterone-regulated gene in the mouse uterus.
    Mol Endocrinol. 1995 Jun;9(6):691-705 PMID: 8592515
  16. Cloning of a novel receptor expressed in rat prostate and ovary.
    Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5925-30 PMID: 8650195
  17. Cellular distribution and gene regulation of estrogen receptors alpha and beta in the rat pituitary gland.
    Endocrinology. 1998 Sep;139(9):3976-83 PMID: 9724053
  18. Analysis of transcription and estrogen insensitivity in the female mouse after targeted disruption of the estrogen receptor gene.
    Mol Endocrinol. 1995 Nov;9(11):1441-54 PMID: 8584021
  19. Expression of betacellulin and epiregulin genes in the mouse uterus temporally by the blastocyst solely at the site of its apposition is coincident with the "window" of implantation.
    Dev Biol. 1997 Oct 15;190(2):178-90 PMID: 9344537
  20. Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse.
    Mol Endocrinol. 1999 Jun;13(6):1005-17 PMID: 10379898
  21. Differential expression of the erbB2 gene in the periimplantation mouse uterus: potential mediator of signaling by epidermal growth factor-like growth factors.
    Endocrinology. 1997 Mar;138(3):1328-37 PMID: 9048643
  22. The inhibition by progesterone of uterine epithelial proliferation in the mouse.
    J Endocrinol. 1973 Jun;57(3):549-54 PMID: 4715727
  23. Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility.
    Endocrinology. 1996 Nov;137(11):4796-805 PMID: 8895349
  24. Nuclear receptors enhance our understanding of transcription regulation.
    Trends Genet. 1988 Nov;4(11):309-14 PMID: 2853466
  25. Molecular cloning, structure, and expression of mouse estrogen-responsive finger protein Efp. Co-localization with estrogen receptor mRNA in target organs.
    J Biol Chem. 1995 Oct 13;270(41):24406-13 PMID: 7592654
  26. Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.
    Genes Dev. 1995 Sep 15;9(18):2266-78 PMID: 7557380
  27. erbB genes in the mouse uterus: cell-specific signaling by epidermal growth factor (EGF) family of growth factors during implantation.
    Dev Biol. 1998 Dec 1;204(1):97-110 PMID: 9851845
  28. Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium.
    Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6535-40 PMID: 9177253
  29. Leukemia inhibitory factor is expressed by the preimplantation uterus and selectively blocks primitive ectoderm formation in vitro.
    Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8240-4 PMID: 1518852
  30. Molecular mechanisms of action of steroid/thyroid receptor superfamily members.
    Annu Rev Biochem. 1994;63:451-86 PMID: 7979245
  31. Specific modulation of estrogen receptor mRNA isoforms in rat pituitary throughout the estrous cycle and in response to steroid hormones.
    Mol Cell Endocrinol. 1997 Aug 8;131(2):147-55 PMID: 9296373
  32. Expression and steroid hormonal control of Muc-1 in the mouse uterus.
    Endocrinology. 1995 Aug;136(8):3639-47 PMID: 7628404
  33. Estrogen and progestin receptors in the macaque endometrium.
    Ann N Y Acad Sci. 1991;622:149-66 PMID: 2064178
  34. Blastocyst's state of activity determines the "window" of implantation in the receptive mouse uterus.
    Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10159-62 PMID: 8234270
  35. Heparin-binding EGF-like growth factor gene is induced in the mouse uterus temporally by the blastocyst solely at the site of its apposition: a possible ligand for interaction with blastocyst EGF-receptor in implantation.
    Development. 1994 May;120(5):1071-83 PMID: 8026321
  36. Mutual and intercompartmental regulation of estrogen receptor and progesterone receptor expression in the mouse uterus.
    Biol Reprod. 1998 Nov;59(5):1143-52 PMID: 9780321
  37. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta.
    Endocrinology. 1997 Mar;138(3):863-70 PMID: 9048584
  38. Expression of insulin-like growth factor-I (IGF-I) and its receptor in the peri-implantation mouse uterus, and cell-specific regulation of IGF-I gene expression by estradiol and progesterone.
    Biol Reprod. 1992 Feb;46(2):208-19 PMID: 1311209
  39. Progesterone and oestrogen receptors in the decidualized mouse uterus and effects of different types of anti-progesterone treatment.
    J Reprod Fertil. 1995 Nov;105(2):215-20 PMID: 8568763
  40. Behavioral effects of estrogen receptor gene disruption in male mice.
    Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1476-81 PMID: 9037078
  41. Progesterone-mediated suppression of estradiol receptors in cynomolgus macaque cervix, endometrium and oviduct during sequential estradiol-progesterone treatment.
    J Steroid Biochem. 1985 Jan;22(1):29-37 PMID: 3974227
  42. Estrogen receptor alpha and progesterone receptor in the rhesus endometrium during the late secretory phase and menses.
    Proc Soc Exp Biol Med. 1998 Sep;218(4):316-21 PMID: 9714074
  43. Creatine kinase activity as an indicator of unopposed estrogen action in the mouse uterus associated with anti-progesterone treatment.
    J Steroid Biochem Mol Biol. 1994 Jun;49(2-3):123-9 PMID: 8031708
  44. The A and B forms of the chicken progesterone receptor arise by alternate initiation of translation of a unique mRNA.
    Biochem Biophys Res Commun. 1987 Dec 16;149(2):493-501 PMID: 3426587
  45. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B.
    EMBO J. 1990 May;9(5):1603-14 PMID: 2328727
  46. Isolation of full-length putative rat lysophospholipase cDNA using improved methods for mRNA isolation and cDNA cloning.
    Biochemistry. 1987 Mar 24;26(6):1617-25 PMID: 3593682
  47. Uterine expression of leukemia inhibitory factor coincides with the onset of blastocyst implantation.
    Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11408-12 PMID: 1722331
  48. Disruption of estrogen signaling does not prevent progesterone action in the estrogen receptor alpha knockout mouse uterus.
    Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3646-51 PMID: 10097091
  49. Cell-type-specific expression of transforming growth factor-alpha in the mouse uterus during the peri-implantation period.
    Biol Reprod. 1991 Aug;45(2):365-72 PMID: 1686188
  50. Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression.
    Development. 1996 Sep;122(9):2687-96 PMID: 8787743
  51. Immunocytochemical analysis of estrogen and progestin receptors in uteri of steroid-treated and pregnant cats.
    Biol Reprod. 1992 Dec;47(6):1073-81 PMID: 1493171
  52. Differential expression of epidermal growth factor receptor (EGF-R) gene and regulation of EGF-R bioactivity by progesterone and estrogen in the adult mouse uterus.
    Endocrinology. 1994 Feb;134(2):971-81 PMID: 7507841
  53. Progesterone regulation of heparin-binding epidermal growth factor-like growth factor gene expression during sensitization and decidualization in the rat uterus: effects of the antiprogestin, ZK 98.299.
    Endocrinology. 1994 Sep;135(3):1256-63 PMID: 8070371
  54. Abdominal B (AbdB) Hoxa genes: regulation in adult uterus by estrogen and progesterone and repression in müllerian duct by the synthetic estrogen diethylstilbestrol (DES).
    Dev Biol. 1998 May 15;197(2):141-54 PMID: 9630742
  55. Developmental pattern of estrogen receptor expression in female mouse genital tracts.
    Endocrinology. 1989 Dec;125(6):2888-96 PMID: 2583044
  56. The novel estrogen receptor-beta subtype: potential role in the cell- and promoter-specific actions of estrogens and anti-estrogens.
    FEBS Lett. 1997 Jun 23;410(1):87-90 PMID: 9247129
  57. Progesterone-binding components of chick oviduct. IV. Characterization of purified subunits.
    J Biol Chem. 1972 Jan 10;247(1):51-9 PMID: 5017767
  58. Steroid hormone receptors: many actors in search of a plot.
    Cell. 1995 Dec 15;83(6):851-7 PMID: 8521509
  59. Immunocytochemical localization of estrogen and progestin receptors in the baboon (Papio anubis) uterus during implantation and pregnancy.
    Endocrinology. 1992 Apr;130(4):2343-53 PMID: 1372241
  60. Subcellular compartmentalization of the progesterone receptor in cat uteri following the acute administration of progesterone.
    Biol Reprod. 1983 Apr;28(3):545-50 PMID: 6850032
  61. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene.
    Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11162-6 PMID: 8248223
  62. Generation and reproductive phenotypes of mice lacking estrogen receptor beta.
    Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15677-82 PMID: 9861029
Article Info
Journal
Endocrinology
Abbr.
Endocrinology
ISSN
0013-7227
DOI
10.1210/endo.140.11.7148
Published
1999-11-00
Pages
5310-21
Language
English
Region
United States
NLM ID
0375040
PMCID
PMC4280800
Subset
IM
Grants
NICHD NIH HHS · P30 HD033994 · United States
NICHD NIH HHS · R37 HD012304 · United States
NIEHS NIH HHS · R01 ES007814 · United States
NICHD NIH HHS · U54 HD033994 · United States
NICHD NIH HHS · HD-29968 · United States
NICHD NIH HHS · HD-12304 · United States
NIEHS NIH HHS · ES-07814 · United States
NICHD NIH HHS · P30 HD002528 · United States
External Links
PubMed source DOI: 10.1210/endo.140.11.7148 PMC Full Text View journal details
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