Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1990 Feb 1;110(2):269–282. doi: 10.1083/jcb.110.2.269

Modulation of gap junction transcript and protein expression during pregnancy in the rat

PMCID: PMC2116004  PMID: 1688855

Abstract

The expression of three different gap junction transcripts, alpha 1 (Cx43), beta 1 (Cx32), and beta 2 (Cx26) was examined in several organs during pregnancy in the rat. In all of the organs that were examined-- uterus, ovary, heart, and liver--there was a strong correlation between levels of gap junction mRNA and gap junction antigens that were detected at different stages of pregnancy. A striking change in alpha 1 transcript levels (a 5.5-fold increase) was detected in the uterine myometrium on the day before parturition. This elevation of the alpha 1 transcript is thought to be associated with the formation of gap junctions that are required for synchronizing the contractility of the myometrial cells during parturition. 2 d before parturition, there was a detectable elevation of beta 2 transcripts and protein in the endometrial epithelium, which was then followed by a dramatic decrease in beta 2 gap junctional protein on the day before parturition. There was also a substantial elevation of alpha 1 transcripts (a 6.7-fold increase) in the stromal regions of the ovary on the day before parturition that was identical to the temporal pattern of alpha 1 expression in the myometrium. In all three instances--the alpha 1 transcripts in the myometrium, beta 2 transcripts in the endometrium, and alpha 1 transcripts in the ovary--the transcript modulation appeared to be cell specific, because the changes in transcript levels of these three gene products occurred independently of the poly(A) + RNA concentrations at the same pregnancy stages in the respective organs. There were no specific changes detected in gap junction transcript levels in the heart and liver during pregnancy. These observations indicate that a cell-specific modulation of gap junction expression occurs in two regions of the uterus and the ovary during pregnancy. Further, it appears that the same gap junction gene in different organs, such as the alpha 1 gene in the uterine myometrium and the heart, can be differentially regulated.

Full Text

The Full Text of this article is available as a PDF (4.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
  2. Beyer E. C., Kistler J., Paul D. L., Goodenough D. A. Antisera directed against connexin43 peptides react with a 43-kD protein localized to gap junctions in myocardium and other tissues. J Cell Biol. 1989 Feb;108(2):595–605. doi: 10.1083/jcb.108.2.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beyer E. C., Paul D. L., Goodenough D. A. Connexin43: a protein from rat heart homologous to a gap junction protein from liver. J Cell Biol. 1987 Dec;105(6 Pt 1):2621–2629. doi: 10.1083/jcb.105.6.2621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burghardt R. C., Matheson R. L., Gaddy D. Gap junction modulation in rat uterus. I. Effects of estrogens on myometrial and serosal cells. Biol Reprod. 1984 Feb;30(1):239–248. doi: 10.1095/biolreprod30.1.239. [DOI] [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Dahl G., Berger W. Nexus formation in the myometrium during parturition and induced by estrogen. Cell Biol Int Rep. 1978 Jul;2(4):381–387. doi: 10.1016/0309-1651(78)90024-3. [DOI] [PubMed] [Google Scholar]
  7. Darnell J. E., Jr Variety in the level of gene control in eukaryotic cells. Nature. 1982 Jun 3;297(5865):365–371. doi: 10.1038/297365a0. [DOI] [PubMed] [Google Scholar]
  8. Dupont E., el Aoumari A., Roustiau-Sévère S., Briand J. P., Gros D. Immunological characterization of rat cardiac gap junctions: presence of common antigenic determinants in heart of other vertebrate species and in various organs. J Membr Biol. 1988 Sep;104(2):119–128. doi: 10.1007/BF01870924. [DOI] [PubMed] [Google Scholar]
  9. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garfield R. E., Puri C. P., Csapo A. I. Endocrine, structural, and functional changes in the uterus during premature labor. Am J Obstet Gynecol. 1982 Jan 1;142(1):21–27. doi: 10.1016/s0002-9378(16)32279-7. [DOI] [PubMed] [Google Scholar]
  11. Garfield R. E., Sims S. M., Kannan M. S., Daniel E. E. Possible role of gap junctions in activation of myometrium during parturition. Am J Physiol. 1978 Nov;235(5):C168–C179. doi: 10.1152/ajpcell.1978.235.5.C168. [DOI] [PubMed] [Google Scholar]
  12. Garfield R. E., Sims S., Daniel E. E. Gap junctions: their presence and necessity in myometrium during parturition. Science. 1977 Dec 2;198(4320):958–960. doi: 10.1126/science.929182. [DOI] [PubMed] [Google Scholar]
  13. Gilula N. B., Epstein M. L., Beers W. H. Cell-to-cell communication and ovulation. A study of the cumulus-oocyte complex. J Cell Biol. 1978 Jul;78(1):58–75. doi: 10.1083/jcb.78.1.58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gilula N. B., Reeves O. R., Steinbach A. Metabolic coupling, ionic coupling and cell contacts. Nature. 1972 Feb 4;235(5336):262–265. doi: 10.1038/235262a0. [DOI] [PubMed] [Google Scholar]
  15. Gimlich R. L., Kumar N. M., Gilula N. B. Sequence and developmental expression of mRNA coding for a gap junction protein in Xenopus. J Cell Biol. 1988 Sep;107(3):1065–1073. doi: 10.1083/jcb.107.3.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goodenough D. A., Paul D. L., Jesaitis L. Topological distribution of two connexin32 antigenic sites in intact and split rodent hepatocyte gap junctions. J Cell Biol. 1988 Nov;107(5):1817–1824. doi: 10.1083/jcb.107.5.1817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  18. Harley C. B. Hybridization of oligo(dT) to RNA on nitrocellulose. Gene Anal Tech. 1987 Mar-Apr;4(2):17–22. doi: 10.1016/0735-0651(87)90013-6. [DOI] [PubMed] [Google Scholar]
  19. Hertzberg E. L. A detergent-independent procedure for the isolation of gap junctions from rat liver. J Biol Chem. 1984 Aug 10;259(15):9936–9943. [PubMed] [Google Scholar]
  20. Hertzberg E. L., Disher R. M., Tiller A. A., Zhou Y., Cook R. G. Topology of the Mr 27,000 liver gap junction protein. Cytoplasmic localization of amino- and carboxyl termini and a hydrophilic domain which is protease-hypersensitive. J Biol Chem. 1988 Dec 15;263(35):19105–19111. [PubMed] [Google Scholar]
  21. Ikeda M., Shibata Y., Yamamoto T. Rapid formation of myometrial gap junctions during parturition in the unilaterally implanted rat uterus. Cell Tissue Res. 1987 May;248(2):297–303. doi: 10.1007/BF00218196. [DOI] [PubMed] [Google Scholar]
  22. Kistler J., Christie D., Bullivant S. Homologies between gap junction proteins in lens, heart and liver. Nature. 1988 Feb 25;331(6158):721–723. doi: 10.1038/331721a0. [DOI] [PubMed] [Google Scholar]
  23. Kumar N. M., Gilula N. B. Cloning and characterization of human and rat liver cDNAs coding for a gap junction protein. J Cell Biol. 1986 Sep;103(3):767–776. doi: 10.1083/jcb.103.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  25. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  26. Larsen W. J., Tung H. N., Polking C. Response of granulosa cell gap junctions to human chorionic gonadotropin (hCG) at ovulation. Biol Reprod. 1981 Dec;25(5):1119–1134. doi: 10.1095/biolreprod25.5.1119. [DOI] [PubMed] [Google Scholar]
  27. Larsen W. J., Wert S. E., Brunner G. D. A dramatic loss of cumulus cell gap junctions is correlated with germinal vesicle breakdown in rat oocytes. Dev Biol. 1986 Feb;113(2):517–521. doi: 10.1016/0012-1606(86)90187-9. [DOI] [PubMed] [Google Scholar]
  28. Loewenstein W. R. Junctional intercellular communication: the cell-to-cell membrane channel. Physiol Rev. 1981 Oct;61(4):829–913. doi: 10.1152/physrev.1981.61.4.829. [DOI] [PubMed] [Google Scholar]
  29. Manjunath C. K., Page E. Rat heart gap junctions as disulfide-bonded connexon multimers: their depolymerization and solubilization in deoxycholate. J Membr Biol. 1986;90(1):43–57. doi: 10.1007/BF01869685. [DOI] [PubMed] [Google Scholar]
  30. Milks L. C., Kumar N. M., Houghten R., Unwin N., Gilula N. B. Topology of the 32-kd liver gap junction protein determined by site-directed antibody localizations. EMBO J. 1988 Oct;7(10):2967–2975. doi: 10.1002/j.1460-2075.1988.tb03159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nicholson B., Dermietzel R., Teplow D., Traub O., Willecke K., Revel J. P. Two homologous protein components of hepatic gap junctions. Nature. 1987 Oct 22;329(6141):732–734. doi: 10.1038/329732a0. [DOI] [PubMed] [Google Scholar]
  32. Palmiter R. D. Ovalbumin messenger ribonucleic acid translation. Comparable rates of polypeptide initiation and elongation on ovalbumin and globin messenger ribonucleic acid in a rabbit reticulocyte lysate. J Biol Chem. 1973 Mar 25;248(6):2095–2106. [PubMed] [Google Scholar]
  33. Paul D. L. Molecular cloning of cDNA for rat liver gap junction protein. J Cell Biol. 1986 Jul;103(1):123–134. doi: 10.1083/jcb.103.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Puri C. P., Garfield R. E. Changes in hormone levels and gap junctions in the rat uterus during pregnancy and parturition. Biol Reprod. 1982 Nov;27(4):967–975. doi: 10.1095/biolreprod27.4.967. [DOI] [PubMed] [Google Scholar]
  35. Saito Y., Sakamoto H., MacLusky N. J., Naftolin F. Gap junctions and myometrial steroid hormone receptors in pregnant and postpartum rats: a possible cellular basis for the progesterone withdrawal hypothesis. Am J Obstet Gynecol. 1985 Mar 15;151(6):805–812. doi: 10.1016/0002-9378(85)90525-3. [DOI] [PubMed] [Google Scholar]
  36. Tabor S., Richardson C. C. DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4767–4771. doi: 10.1073/pnas.84.14.4767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Winterhager E., Brümmer F., Dermietzel R., Hülser D. F., Denker H. W. Gap junction formation in rabbit uterine epithelium in response to embryo recognition. Dev Biol. 1988 Mar;126(1):203–211. doi: 10.1016/0012-1606(88)90254-0. [DOI] [PubMed] [Google Scholar]
  39. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  40. Yancey S. B., John S. A., Lal R., Austin B. J., Revel J. P. The 43-kD polypeptide of heart gap junctions: immunolocalization, topology, and functional domains. J Cell Biol. 1989 Jun;108(6):2241–2254. doi: 10.1083/jcb.108.6.2241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zimmer D. B., Green C. R., Evans W. H., Gilula N. B. Topological analysis of the major protein in isolated intact rat liver gap junctions and gap junction-derived single membrane structures. J Biol Chem. 1987 Jun 5;262(16):7751–7763. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES