Skip to main content
SpringerLink
Log in

Inhibin/activin subunits alpha, beta-A and beta-B are differentially expressed in normal human endometrium throughout the menstrual cycle

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Inhibins are dimeric glycoproteins composed of an alpha (α) subunit and one of two possible beta (β-) subunits (βA or βB). The aims of this study were to assess the frequency and tissue distribution patterns of the inhibin subunits in normal human endometrium. Samples from human endometrium from proliferative phase (PP; n=32), early secretory phase (ES; n=10) and late secretory phase (LS; n=12) were obtained. Immunohistochemistry, immunofluorescence and a statistical analysis were performed. All three inhibin subunits were expressed by normal endometrium by immunohistochemistry and immunofluorescence. Inhibin-α was primarily detected in glandular epithelial cells, while inhibin-β subunits were additionally localised in stromal tissue. Inhibin-α staining reaction increased significantly between PP and ES (P<0.05), PP and LS (P<0.01), and ES and LS (P<0.02). Inhibin-βA and -βB were significant higher in LS than PP (P<0.05) and LS than ES (P<0.05). All three inhibin subunits were expressed by human endometrium varying across the menstrual cycle. This suggests substantial functions in human implantation of inhibin-α subunit, while stromal expression of the β subunits could be important in the paracrine signalling for adequate endometrial maturation. The distinct expression in human endometrial tissue suggests a synthesis of inhibins into the lumen and a predominant secretion of activins into the stroma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2a–c
Fig. 3a–f
Fig. 4a–d
Fig. 5a–d
Fig. 6a–d
Fig. 7
Fig. 8a–f
Fig. 9a–f

Similar content being viewed by others

References

  • Caniggia I, Lye SJ, Cross JC (1997) Activin is a local regulator of human cytotrophoblast cell differentiation. Endocrinology 138:3976–3986

    Article  CAS  PubMed  Google Scholar 

  • Chabbert Buffet N, Djakoure C, Maitre SC, Bouchard P (1998) Regulation of the human menstrual cycle. Front Neuroendocrinol 19:151–186

    Article  PubMed  Google Scholar 

  • Chong H, Pangas SA, Bernard DJ, Wang E, Gitch J, Chen W, Draper LB, Cox ET, Woodruff TK (2000) Structure and expression of a membrane component of the inhibin receptor system. Endocrinology 141:2600–2607

    Article  CAS  PubMed  Google Scholar 

  • Dallenbach-Hellweg G, Poulsen H (1985) Atlas der Histopathologie des Endometriums. Springer Berlin, Heidelberg, New York

  • de Kretser DM, Hedger MP, Loveland KL, Phillips DJ (2002) Inhibins, activins and follistatin in reproduction. Hum Reprod Update 8:529–541

    Article  PubMed  Google Scholar 

  • Fang J, Yin W, Smiley E, Wang SQ, Bonadio J (1996) Molecular cloning of the mouse activin beta E subunit gene. Biochem Biophys Res Commun 228:669–674

    Article  CAS  PubMed  Google Scholar 

  • Fowler PA, Evans LW, Groome NP, Templeton A, Knight PG (1998) A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy. Hum Reprod 13:3530–3536

    Article  CAS  PubMed  Google Scholar 

  • Groome N, Lawrence M (1991) Preparation of monoclonal antibodies to the beta A subunit of ovarian inhibin using a synthetic peptide immunogen. Hybridoma 10:309–316

    CAS  PubMed  Google Scholar 

  • Groome N, Hancock J, Betteridge A, Lawrence M, Craven R (1990) Monoclonal and polyclonal antibodies reactive with the 1–32 amino terminal sequence of the alpha subunit of human 32 K inhibin. Hybridoma 9:31–42

    CAS  PubMed  Google Scholar 

  • Hötten G, Neidhardt H, Schneider C, Pohl J (1995) Cloning of a new member of the TGF-beta family: a putative new activin beta C chain. Biochem Biophys Res Commun 206:608–613

    Article  PubMed  Google Scholar 

  • Jeschke U, Richter DU, Hammer A, Briese V, Friese K, Karsten U (2002) Expression of the Thomsen-Friedenreich antigen and of its putative carrier protein mucin 1 in the human placenta and in trophoblast cells in vitro. Histochem Cell Biol 117:219–226

    Article  CAS  PubMed  Google Scholar 

  • Jones RL, Salamonsen LA, Critchley HO, Rogers PA, Affandi B, Findlay JK (2000) Inhibin and activin subunits are differentially expressed in endometrial cells and leukocytes during the menstrual cycle, in early pregnancy and in women using progestin-only contraception. Mol Hum Reprod 6:1107–1117

    Article  CAS  PubMed  Google Scholar 

  • Jones RL, Salamonsen LA, Findlay JK (2002) Activin A promotes human endometrial stromal cell decidualization in vitro. J Clin Endocrinol Metab 87:4001–4004

    Article  CAS  PubMed  Google Scholar 

  • Kalkhoven E, Roelen BA, de Winter JP, Mummery CL, van den Eijnden-van Raaij AJ, van der Saag PT, van der Burg B (1995) Resistance to transforming growth factor beta and activin due to reduced receptor expression in human breast tumor cell lines. Cell Growth Differ 6:1151–1161

    CAS  PubMed  Google Scholar 

  • Keelan JA, Zhou RL, Mitchell MD (2000) Activin A exerts both pro- and anti-inflammatory effects on human term gestational tissues. Placenta 21:38–43

    Article  CAS  PubMed  Google Scholar 

  • Leung PH, Salamonsen LA, Findlay JK (1998) Immunolocalization of inhibin and activin subunits in human endometrium across the menstrual cycle. Hum Reprod 13:3469–3477

    Article  CAS  PubMed  Google Scholar 

  • Lewis KA, Gray PC, Blount AL, MacConell LA, Wiater E, Bilezikjian LM, Vale W (2000) Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature 404:411–414

    Article  CAS  PubMed  Google Scholar 

  • Li Q, Karam SM, Coerver KA, Matzuk MM, Gordon JI (1998) Stimulation of activin receptor II signaling pathways inhibits differentiation of multiple gastric epithelial lineages. Mol Endocrinol 12:181–192

    Article  PubMed  Google Scholar 

  • Matzuk MM, Finegold MJ, Su JG, Hsueh AJ, Bradley A (1992) Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 360:313–319

    Article  CAS  PubMed  Google Scholar 

  • McCarthy SA, Bicknell R (1993) Inhibition of vascular endothelial cell growth by activin-A. J Biol Chem 268:23066–23071

    CAS  PubMed  Google Scholar 

  • Munz B, Hubner G, Tretter Y, Alzheimer C, Werner S (1999) A novel role of activin in inflammation and repair. J Endocrinol 161:187–193

    CAS  PubMed  Google Scholar 

  • Mylonas I, Speer R, Makovitzky J, Richter DU, Briese V, Jeschke U, Friese K (2000) Immunohistochemical analysis of steroid receptors and glycodelin A (PP14) in isolated glandular epithelial cells of normal human endometrium. Histochem Cell Biol 114:405–411

    CAS  PubMed  Google Scholar 

  • Mylonas I, Jeschke U, Winkler L, Makovitzky J, Richter DU, Briese V, Friese K (2003a) Immunohistochemical expression of inhibin-alpha in human endometrium and the in vitro secretion of inhibin, estradiol and cortisol in cultured human endometrial glandular cells. Arch Gynecol Obstet 268:142–150

    Google Scholar 

  • Mylonas I, Winkler L, Jeschke U, Briese V, Friese K (2003b) Investigations on isolation, purification and cultivation of human endometrial cells and on the in vitro inhibin expression in glandular epithelial cells. Zentralbl Gynakol 125:415–423

    Article  CAS  PubMed  Google Scholar 

  • Mylonas I, Makovitzky J, Richter DU, Jeschke U, Briese V, Friese K (2004) Expression of the inhibin-alpha subunit in normal, hyperplastic and malignant endometrial tissue: an immunohistochemical analysis. Gynecol Oncol 93:92–97

    Google Scholar 

  • Ni X, Luo S, Minegishi T, Peng C (2000) Activin A in JEG-3 cells: potential role as an autocrine regulator of steroidogenesis in humans. Biol Reprod 62:1224–1230

    CAS  PubMed  Google Scholar 

  • Oda S, Nishimatsu S, Murakami K, Ueno N (1995) Molecular cloning and functional analysis of a new activin beta subunit: a dorsal mesoderm-inducing activity in Xenopus. Biochem Biophys Res Commun 210:581–588

    Article  CAS  PubMed  Google Scholar 

  • Otani T, Minami S, Kokawa K, Shikone T, Yamoto M, Nakano R (1998) Immunohistochemical localization of activin A in human endometrial tissues during the menstrual cycle and in early pregnancy. Obstet Gynecol 91:685–692

    Article  CAS  PubMed  Google Scholar 

  • Petraglia F (1997) Inhibin, activin and follistatin in the human placenta: a new family of regulatory proteins. Placenta 18:3–8

    Article  CAS  PubMed  Google Scholar 

  • Petraglia F, Florio P, Luisi S, Gallo R, Gadducci A, Vigano P, Di Blasio AM, Genazzani AR, Vale W (1998) Expression and secretion of inhibin and activin in normal and neoplastic uterine tissues. High levels of serum activin A in women with endometrial and cervical carcinoma. J Clin Endocrinol Metab 83:1194–1200

    Article  CAS  PubMed  Google Scholar 

  • Remmele W, Stegner HE (1987) Vorschlag zur einheitlichen Definierung eines immunreaktiven Score (IRS) für den immunhistochemischen Östrogenrezeptornachweis (ER-ICA) im Mammakarzinomgewebe. Pathologe 8:138–140

    CAS  PubMed  Google Scholar 

  • Riley SC, Leask R, Balfour C, Brennand JE, Groome NP (2000) Production of inhibin forms by the fetal membranes, decidua, placenta and fetus at parturition. Hum Reprod 15:578–583

    Article  CAS  PubMed  Google Scholar 

  • Risbridger GP, Schmitt JF, Robertson DM (2001) Activins and inhibins in endocrine and other tumors. Endocr Rev 22:836–858

    Article  CAS  PubMed  Google Scholar 

  • Robertson DM, Hertan R, Farnworth PG (2000) Is the action of inhibin mediated via a unique receptor? Rev Reprod 5:131–135

    Article  CAS  PubMed  Google Scholar 

  • Robinson GW, Hennighausen L (1997) Inhibins and activins regulate mammary epithelial cell differentiation through mesenchymal-epithelial interactions. Development 124:2701–2708

    CAS  PubMed  Google Scholar 

  • Smith JC, Price BM, Van Nimmen K, Huylebroeck D (1990) Identification of a potent Xenopus mesoderm-inducing factor as a homologue of activin A. Nature 345:729–731

    Article  CAS  PubMed  Google Scholar 

  • Vale W, Rivier C, Hsueh A, Campen C, Meunier H, Bicsak T, Vaughan J, Corrigan A, Bardin W, Sawchenko P, et al (1988) Chemical and biological characterization of the inhibin family of protein hormones. Recent Prog Horm Res 44:1–34

    CAS  PubMed  Google Scholar 

  • Welt CK (2002) The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction. Curr Opin Obstet Gynecol 14:317–323

    Article  PubMed  Google Scholar 

  • Welt C, Sidis Y, Keutmann H, Schneyer A (2002) Activins, inhibins, and follistatins: from endocrinology to signaling. A paradigm for the new millennium. Exp Biol Med (Maywood) 227:724–752

    Google Scholar 

  • Ying SY (1988) Inhibins, activins, and follistatins: gonadal proteins modulating the secretion of follicle-stimulating hormone. Endocr Rev 9:267–293

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank the nurses, medical doctors and laboratory staff for obtaining the endometrial material. This study was supported in part by the FöFoLe project of the Ludwig-Maximilians-University Munich for I. Mylonas.

Author information

Authors and Affiliations

  1. First Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University Munich, Maistrasse 11, 80337, Munich, Germany

    Ioannis Mylonas, Udo Jeschke, Irmgard Wiest, Anna Hoeing, Julia Vogl, Naim Shabani, Christina Kuhn, Sandra Schulze, Markus S. Kupka & Klaus Friese

Authors
  1. Ioannis Mylonas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Udo Jeschke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Irmgard Wiest
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna Hoeing
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julia Vogl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naim Shabani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christina Kuhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sandra Schulze
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Markus S. Kupka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Klaus Friese
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ioannis Mylonas.

Additional information

I. Mylonas and U. Jeschke contributed equally to this work

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mylonas, I., Jeschke, U., Wiest, I. et al. Inhibin/activin subunits alpha, beta-A and beta-B are differentially expressed in normal human endometrium throughout the menstrual cycle. Histochem Cell Biol 122, 461–471 (2000). https://doi.org/10.1007/s00418-004-0709-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-004-0709-6

Keywords

Search

Navigation