Skip to main content
Infectious Diseases in Obstetrics and Gynecology logoLink to Infectious Diseases in Obstetrics and Gynecology
. 1999;7(1-2):5–9. doi: 10.1155/S1064744999000022

Heat shock proteins in human endometrium throughout the menstrual cycle.

S Tabibzadeh 1, J Broome 1
PMCID: PMC1784709  PMID: 10231001

Abstract

Human endometrium, in response to steroid hormones, undergoes characteristic cycles of proliferation, secretory changes, and tissue shedding. Human endometrium expresses a molecular repertoire which includes the heat shock proteins (Hsps) Hsp27, Hsp60, Hsp70, Hsp90, and alpha crystallin B chain. The expression of Hsp27, Hsp60, and the constitutive form of Hsp70 (Hsc70) shows a sharp increase in human endometrium after ovulation. The maximal expression of the molecular chaperone, alpha crystallin B chain, occurs during the secretory phase. In view of known functions of the Hsps, it is likely that these proteins are involved in protection of the endometrial proteins against factors with the potential to lead to protein denaturation. Tumor necrosis factor-alpha (TNF-alpha) is a cytotoxic cytokine that is produced in progressive amounts during the secretory phase. The function of the Hsps may be to protect cells against the cytotoxic damage of TNF-alpha, particularly during the critical period of "implantation window."

Full Text

The Full Text of this article is available as a PDF (494.0 KB).

Selected References

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

  1. Anfinsen C. B. Principles that govern the folding of protein chains. Science. 1973 Jul 20;181(4096):223–230. doi: 10.1126/science.181.4096.223. [DOI] [PubMed] [Google Scholar]
  2. Arrigo A. P., Welch W. J. Characterization and purification of the small 28,000-dalton mammalian heat shock protein. J Biol Chem. 1987 Nov 15;262(32):15359–15369. [PubMed] [Google Scholar]
  3. Bagchi M. K., Tsai S. Y., Tsai M. J., O'Malley B. W. Progesterone enhances target gene transcription by receptor free of heat shock proteins hsp90, hsp56, and hsp70. Mol Cell Biol. 1991 Oct;11(10):4998–5004. doi: 10.1128/mcb.11.10.4998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baniahmad A., Tsai M. J. Mechanisms of transcriptional activation by steroid hormone receptors. J Cell Biochem. 1993 Feb;51(2):151–156. doi: 10.1002/jcb.240510206. [DOI] [PubMed] [Google Scholar]
  5. Bayard F., Damilano S., Robel P., Baulieu E. E. Cytoplasmic and nuclear estradiol and progesterone receptors in human endometrium. J Clin Endocrinol Metab. 1978 Apr;46(4):635–648. doi: 10.1210/jcem-46-4-635. [DOI] [PubMed] [Google Scholar]
  6. Bhat S. P., Horwitz J., Srinivasan A., Ding L. Alpha B-crystallin exists as an independent protein in the heart and in the lens. Eur J Biochem. 1991 Dec 18;202(3):775–781. doi: 10.1111/j.1432-1033.1991.tb16432.x. [DOI] [PubMed] [Google Scholar]
  7. Bulmer J. N., Morrison L., Longfellow M., Ritson A., Pace D. Granulated lymphocytes in human endometrium: histochemical and immunohistochemical studies. Hum Reprod. 1991 Jul;6(6):791–798. doi: 10.1093/oxfordjournals.humrep.a137430. [DOI] [PubMed] [Google Scholar]
  8. Craig E. A., Weissman J. S., Horwich A. L. Heat shock proteins and molecular chaperones: mediators of protein conformation and turnover in the cell. Cell. 1994 Aug 12;78(3):365–372. doi: 10.1016/0092-8674(94)90416-2. [DOI] [PubMed] [Google Scholar]
  9. Ellis J. Proteins as molecular chaperones. 1987 Jul 30-Aug 5Nature. 328(6129):378–379. doi: 10.1038/328378a0. [DOI] [PubMed] [Google Scholar]
  10. Ellis R. J., van der Vies S. M. Molecular chaperones. Annu Rev Biochem. 1991;60:321–347. doi: 10.1146/annurev.bi.60.070191.001541. [DOI] [PubMed] [Google Scholar]
  11. Fouqueray B., Philippe C., Amrani A., Perez J., Baud L. Heat shock prevents lipopolysaccharide-induced tumor necrosis factor-alpha synthesis by rat mononuclear phagocytes. Eur J Immunol. 1992 Nov;22(11):2983–2987. doi: 10.1002/eji.1830221133. [DOI] [PubMed] [Google Scholar]
  12. Frederikse P. H., Dubin R. A., Haynes J. I., 2nd, Piatigorsky J. Structure and alternate tissue-preferred transcription initiation of the mouse alpha B-crystallin/small heat shock protein gene. Nucleic Acids Res. 1994 Dec 25;22(25):5686–5694. doi: 10.1093/nar/22.25.5686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fuqua S. A., Blum-Salingaros M., McGuire W. L. Induction of the estrogen-regulated "24K" protein by heat shock. Cancer Res. 1989 Aug 1;49(15):4126–4129. [PubMed] [Google Scholar]
  14. Gruidl M., Buyuksal A., Babaknia A., Fazleabas A. T., Sivarajah S., Satyaswaroop P. G., Tabibzadeh S. The progressive rise in the expression of alpha crystallin B chain in human endometrium is initiated during the implantation window: modulation of gene expression by steroid hormones. Mol Hum Reprod. 1997 Apr;3(4):333–342. doi: 10.1093/molehr/3.4.333. [DOI] [PubMed] [Google Scholar]
  15. Hall T. J. Role of hsp70 in cytokine production. Experientia. 1994 Nov 30;50(11-12):1048–1053. doi: 10.1007/BF01923460. [DOI] [PubMed] [Google Scholar]
  16. Hirayoshi K., Kudo H., Takechi H., Nakai A., Iwamatsu A., Yamada K. M., Nagata K. HSP47: a tissue-specific, transformation-sensitive, collagen-binding heat shock protein of chicken embryo fibroblasts. Mol Cell Biol. 1991 Aug;11(8):4036–4044. doi: 10.1128/mcb.11.8.4036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Horwitz J. Alpha-crystallin can function as a molecular chaperone. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10449–10453. doi: 10.1073/pnas.89.21.10449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hunt C., Morimoto R. I. Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6455–6459. doi: 10.1073/pnas.82.19.6455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jacquier-Sarlin M. R., Fuller K., Dinh-Xuan A. T., Richard M. J., Polla B. S. Protective effects of hsp70 in inflammation. Experientia. 1994 Nov 30;50(11-12):1031–1038. doi: 10.1007/BF01923458. [DOI] [PubMed] [Google Scholar]
  20. Jakob U., Gaestel M., Engel K., Buchner J. Small heat shock proteins are molecular chaperones. J Biol Chem. 1993 Jan 25;268(3):1517–1520. [PubMed] [Google Scholar]
  21. Jindal S., Dudani A. K., Singh B., Harley C. B., Gupta R. S. Primary structure of a human mitochondrial protein homologous to the bacterial and plant chaperonins and to the 65-kilodalton mycobacterial antigen. Mol Cell Biol. 1989 May;9(5):2279–2283. doi: 10.1128/mcb.9.5.2279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jättelä M. Overexpression of major heat shock protein hsp70 inhibits tumor necrosis factor-induced activation of phospholipase A2. J Immunol. 1993 Oct 15;151(8):4286–4294. [PubMed] [Google Scholar]
  23. Jättelä M., Wissing D. Emerging role of heat shock proteins in biology and medicine. Ann Med. 1992 Aug;24(4):249–258. doi: 10.3109/07853899209149952. [DOI] [PubMed] [Google Scholar]
  24. Klemenz R., Andres A. C., Fröhli E., Schäfer R., Aoyama A. Expression of the murine small heat shock proteins hsp 25 and alpha B crystallin in the absence of stress. J Cell Biol. 1993 Feb;120(3):639–645. doi: 10.1083/jcb.120.3.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Klemenz R., Fröhli E., Steiger R. H., Schäfer R., Aoyama A. Alpha B-crystallin is a small heat shock protein. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3652–3656. doi: 10.1073/pnas.88.9.3652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Koshiyama M., Konishi I., Nanbu K., Nanbu Y., Mandai M., Komatsu T., Yamamoto S., Mori T., Fujii S. Immunohistochemical localization of heat shock proteins HSP70 and HSP90 in the human endometrium: correlation with sex steroid receptors and Ki-67 antigen expression. J Clin Endocrinol Metab. 1995 Apr;80(4):1106–1112. doi: 10.1210/jcem.80.4.7714077. [DOI] [PubMed] [Google Scholar]
  27. Lindquist S., Craig E. A. The heat-shock proteins. Annu Rev Genet. 1988;22:631–677. doi: 10.1146/annurev.ge.22.120188.003215. [DOI] [PubMed] [Google Scholar]
  28. Mehlen P., Mehlen A., Guillet D., Preville X., Arrigo A. P. Tumor necrosis factor-alpha induces changes in the phosphorylation, cellular localization, and oligomerization of human hsp27, a stress protein that confers cellular resistance to this cytokine. J Cell Biochem. 1995 Jun;58(2):248–259. doi: 10.1002/jcb.240580213. [DOI] [PubMed] [Google Scholar]
  29. Nip M. M., Miller D., Taylor P. V., Gannon M. J., Hancock K. W. Expression of heat shock protein 70 kDa in human endometrium of normal and infertile women. Hum Reprod. 1994 Jul;9(7):1253–1256. doi: 10.1093/oxfordjournals.humrep.a138689. [DOI] [PubMed] [Google Scholar]
  30. Quax-Jeuken Y., Quax W., van Rens G., Khan P. M., Bloemendal H. Complete structure of the alpha B-crystallin gene: conservation of the exon-intron distribution in the two nonlinked alpha-crystallin genes. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5819–5823. doi: 10.1073/pnas.82.17.5819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ratajczak T., Carrello A., Mark P. J., Warner B. J., Simpson R. J., Moritz R. L., House A. K. The cyclophilin component of the unactivated estrogen receptor contains a tetratricopeptide repeat domain and shares identity with p59 (FKBP59). J Biol Chem. 1993 Jun 25;268(18):13187–13192. [PubMed] [Google Scholar]
  32. Renoir J. M., Radanyi C., Faber L. E., Baulieu E. E. The non-DNA-binding heterooligomeric form of mammalian steroid hormone receptors contains a hsp90-bound 59-kilodalton protein. J Biol Chem. 1990 Jun 25;265(18):10740–10745. [PubMed] [Google Scholar]
  33. Satyaswaroop P. G., Wartell D. J., Mortel R. Distribution of progesterone receptor, estradiol dehydrogenase, and 20 alpha-dihydroprogesterone dehydrogenase activities in human endometrial glands and stroma: progestin induction of steroid dehydrogenase activities in vitro is restricted to the glandular epithelium. Endocrinology. 1982 Sep;111(3):743–749. doi: 10.1210/endo-111-3-743. [DOI] [PubMed] [Google Scholar]
  34. Snyder Y. M., Guthrie L., Evans G. F., Zuckerman S. H. Transcriptional inhibition of endotoxin-induced monokine synthesis following heat shock in murine peritoneal macrophages. J Leukoc Biol. 1992 Feb;51(2):181–187. doi: 10.1002/jlb.51.2.181. [DOI] [PubMed] [Google Scholar]
  35. Subjeck J. R., Shyy T., Shen J., Johnson R. J. Association between the mammalian 110,000-dalton heat-shock protein and nucleoli. J Cell Biol. 1983 Nov;97(5 Pt 1):1389–1395. doi: 10.1083/jcb.97.5.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tabibzadeh S. S., Bettica A., Gerber M. A. Variable expression of Ia antigens in human endometrium and in chronic endometritis. Am J Clin Pathol. 1986 Aug;86(2):153–160. doi: 10.1093/ajcp/86.2.153. [DOI] [PubMed] [Google Scholar]
  37. Tabibzadeh S., Kong Q. F., Satyaswaroop P. G., Babaknia A. Heat shock proteins in human endometrium throughout the menstrual cycle. Hum Reprod. 1996 Mar;11(3):633–640. doi: 10.1093/humrep/11.3.633. [DOI] [PubMed] [Google Scholar]
  38. Tabibzadeh S., Zupi E., Babaknia A., Liu R., Marconi D., Romanini C. Site and menstrual cycle-dependent expression of proteins of the tumour necrosis factor (TNF) receptor family, and BCL-2 oncoprotein and phase-specific production of TNF alpha in human endometrium. Hum Reprod. 1995 Feb;10(2):277–286. doi: 10.1093/oxfordjournals.humrep.a135928. [DOI] [PubMed] [Google Scholar]
  39. Tseng L., Gurpide E. Effects of progestins on estradiol receptor levels in human endometrium. J Clin Endocrinol Metab. 1975 Aug;41(2):402–404. doi: 10.1210/jcem-41-2-402. [DOI] [PubMed] [Google Scholar]
  40. Wei Y. Q., Zhao X., Kariya Y., Fukata H., Teshigawara K., Uchida A. Induction of apoptosis by quercetin: involvement of heat shock protein. Cancer Res. 1994 Sep 15;54(18):4952–4957. [PubMed] [Google Scholar]

Articles from Infectious Diseases in Obstetrics and Gynecology are provided here courtesy of Wiley

RESOURCES