Skip to main content
SpringerLink
Log in

Sex Steroid Signaling in the Airway

  • Chapter
  • First Online:
Calcium Signaling In Airway Smooth Muscle Cells

  • 1014 Accesses

Abstract

The influence of sex hormones (estrogen, progesterone, testosterone) in the biology and pathophysiology of various organ systems is being increasingly recognized. While sex steroid effects, especially estrogens, on the cardiovascular system have been well studied, clinical and emerging bench research evidence exists for the role of sex hormones in airway and lung physiology and in diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. In this chapter, we briefly define what sex differences exist in airway or lung structure and function under normal conditions, the potential role of sex steroids at different time points in life and in specific disease states, setting the stage to explore whether and how sex hormone signaling mechanisms may be contributory. We focus on the mechanisms by which estrogens, progresterone, and testosterone influence airway smooth muscle and epithelium in regulating airway tone and the potential contribution of these hormones in airway remodeling.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. No authors (2010) Putting gender on the agenda. Nature 465:665. doi: 10.1038/465665a

  2. Miller VM (2010) Sex-based differences in vascular function. Womens Health (Lond Engl) 6:737–52. doi: 10.2217/whe.10.53

    Article  CAS  Google Scholar 

  3. Hepper PG, Shannon EA and Dornan JC (1997) Sex differences in fetal mouth movements. Lancet 350:1820.

    Article  PubMed  CAS  Google Scholar 

  4. Seaborn T, Simard M, Provost PR, Piedboeuf B and Tremblay Y (2010) Sex hormone metabolism in lung development and maturation. Trends Endocrinol Metab 21:729–38.

    Article  PubMed  CAS  Google Scholar 

  5. Becklake MR and Kauffmann F (1999) Gender differences in airway behaviour over the human life span. Thorax 54:1119–38.

    Article  PubMed  CAS  Google Scholar 

  6. Carey MA, Card JW, Voltz JW, Arbes SJ, Jr., Germolec DR, Korach KS and Zeldin DC (2007) It’s all about sex: gender, lung development and lung disease. Trends Endocrinol Metab 18:308–13.

    Article  PubMed  CAS  Google Scholar 

  7. Abramovich DR (1974) Human sexual differentiation–in utero influences. J Obstet Gynaecol Br Commonw 81:448–53.

    Article  PubMed  CAS  Google Scholar 

  8. Kimura Y, Suzuki T, Kaneko C, Darnel AD, Akahira J, Ebina M, Nukiwa T and Sasano H (2003) Expression of androgen receptor and 5alpha-reductase types 1 and 2 in early gestation fetal lung: a possible correlation with branching morphogenesis. Clin Sci (Lond) 105:709–13.

    Article  CAS  Google Scholar 

  9. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F and Kirmeyer S (2006) Births: final data for 2004. Natl Vital Stat Rep 55:1–101.

    Google Scholar 

  10. Townsend EA, Miller VM and Prakash YS (2012) Sex differences and sex steroids in lung health and disease. Endocr Rev 33:1–47. doi: 10.1210/er.2010-0031

    Article  PubMed  CAS  Google Scholar 

  11. Melgert BN, Ray A, Hylkema MN, Timens W and Postma DS (2007) Are there reasons why adult asthma is more common in females? Curr Allergy Asthma Rep 7:143–50.

    Article  PubMed  CAS  Google Scholar 

  12. Postma DS (2007) Gender differences in asthma development and progression. Gend Med 4 Suppl B:S133–46.

    Article  PubMed  Google Scholar 

  13. Schatz M, Dombrowski MP, Wise R, Thom EA, Landon M, Mabie W, Newman RB, Hauth JC, Lindheimer M, Caritis SN, Leveno KJ, Meis P, Miodovnik M, Wapner RJ, Paul RH, Varner MW, O’Sullivan M J, Thurnau GR, Conway D and McNellis D (2003) Asthma morbidity during pregnancy can be predicted by severity classification. J Allergy Clin Immunol 112:283–8.

    Article  PubMed  Google Scholar 

  14. Skobeloff EM, Spivey WH, St Clair SS and Schoffstall JM (1992) The influence of age and sex on asthma admissions. JAMA 268:3437–40.

    Article  PubMed  CAS  Google Scholar 

  15. Carey MA, Card JW, Voltz JW, Germolec DR, Korach KS and Zeldin DC (2007) The impact of sex and sex hormones on lung physiology and disease: lessons from animal studies. Am J Physiol Lung Cell Mol Physiol %R 10.1152/ajplung.00174.2007 293:L272–278.

    Google Scholar 

  16. Dimitropoulou C, White RE, Ownby DR and Catravas JD (2005) Estrogen reduces carbachol-induced constriction of asthmatic airways by stimulating large-conductance voltage and calcium-dependent potassium channels. Am J Respir Cell Mol Biol 32:239–47.

    Article  PubMed  CAS  Google Scholar 

  17. Matsubara S, Swasey CH, Loader JE, Dakhama A, Joetham A, Ohnishi H, Balhorn A, Miyahara N, Takeda K and Gelfand EW (2008) Estrogen determines sex differences in airway responsiveness after allergen exposure. Am J Respir Cell Mol Biol 38:501–8.

    Article  PubMed  CAS  Google Scholar 

  18. Ghayee HK and Auchus RJ (2007) Basic concepts and recent developments in human steroid hormone biosynthesis. Reviews in endocrine & metabolic disorders 8:289–300. doi: 10.1007/s11154-007-9052-2

    Article  CAS  Google Scholar 

  19. Payne AH and Hales DB (2004) Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev 25:947–70.

    Article  PubMed  CAS  Google Scholar 

  20. Luu-The V and Labrie F (2010) The intracrine sex steroid biosynthesis pathways. Prog Brain Res 181:177–92. doi: S0079-6123(08)81010-2 [pii] 10.1016/S0079-6123(08)81010-2

    Google Scholar 

  21. Miller VM and Duckles SP (2008) Vascular actions of estrogens: functional implications. Pharmacol Rev 60:210–41.

    Article  PubMed  CAS  Google Scholar 

  22. Simoncini T and Genazzani AR (2003) Non-genomic actions of sex steroid hormones. Eur J Endocrinol 148:281–92.

    Article  PubMed  CAS  Google Scholar 

  23. Tofovic SP (2010) Estrogens and Development of Pulmonary Hypertension – Interaction of Estradiol Metabolism and Pulmonary Vascular Disease. J Cardiovasc Pharmacol 56:696–708.

    Article  PubMed  CAS  Google Scholar 

  24. Townsend EA, Thompson MA, Pabelick CM and Prakash YS (2010) Rapid effects of estrogen on intracellular Ca2+ regulation in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 298:L521 – 30.

    Article  PubMed  CAS  Google Scholar 

  25. Valverde MA, Rojas P, Amigo J, Cosmelli D, Orio P, Bahamonde MI, Mann GE, Vergara C and Latorre R (1999) Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit. Science 285:1929–31.

    Article  PubMed  CAS  Google Scholar 

  26. Lambert JJ, Belelli D, Peden DR, Vardy AW and Peters JA (2003) Neurosteroid modulation of GABAA receptors. Prog Neurobiol 71:67–80.

    Article  PubMed  CAS  Google Scholar 

  27. Townsend E, Meuchel L, Thompson M, Pabelick C and Prakash Y (2011) Estrogen increased nitric oxide production in human bronchial epithelium. J Pharmacol Exp Therap 339:815–824.

    Article  CAS  Google Scholar 

  28. Hamad AM, Clayton A, Islam B and Knox AJ (2003) Guanylyl cyclases, nitric oxide, natriuretic peptides, and airway smooth muscle function. Am J Physiol Lung Cell Mol Physiol 285:L973 – 83.

    PubMed  CAS  Google Scholar 

  29. Folkerts G and Nijkamp FP (2006) Nitric oxide in asthma therapy. Curr Pharm Des 12:3221–32.

    Article  PubMed  CAS  Google Scholar 

  30. Kirsch EA, Yuhanna IS, Chen Z, German Z, Sherman TS and Shaul PW (1999) Estrogen acutely stimulates endothelial nitric oxide synthase in H441 human airway epithelial cells. Am J Respir Cell Mol Biol 20:658–66.

    Article  PubMed  CAS  Google Scholar 

  31. Jain R, Ray JM, Pan JH and Brody SL (2012) Sex hormone-dependent regulation of cilia beat frequency in airway epithelium. Am J Respir Cell Mol Biol 46:446–53. doi: 10.1165/rcmb.2011-0107OC

    Article  PubMed  CAS  Google Scholar 

  32. Ivanova MM, Mazhawidza W, Dougherty SM and Klinge CM (2010) Sex Differences in Estrogen Receptor Subcellular Location and Activity in Lung Adenocarcinoma Cells. Am. J. Respir. Cell Mol. Biol. 42:320–330.

    Article  PubMed  CAS  Google Scholar 

  33. Pang JJ, Xu XB, Li HF, Zhang XY, Zheng TZ and Qu SY (2002) Inhibition of beta-estradiol on trachea smooth muscle contraction in vitro and in vivo. Acta Pharmacol Sin 23:273–7.

    PubMed  CAS  Google Scholar 

  34. Jia S, Zhang X, He DZ, Segal M, Berro A, Gerson TG, Wang Z and Casale TB (2011) Expression and Function of a Novel Variant of Estrogen Receptor-ER-{alpha}36 in Mouse Airway. Am J Respir Cell Mol Biol. doi: 2010-0268OC [pii] 10.1165/rcmb.2010-0268OC

    Google Scholar 

  35. Foster PS, Goldie RG and Paterson JW (1983) Effect of steroids on beta-adrenoceptor-mediated relaxation of pig bronchus. Br J Pharmacol 78:441–5.

    Article  PubMed  CAS  Google Scholar 

  36. Perusquia M, Hernandez R, Montano LM, Villalon CM and Campos MG (1997) Inhibitory effect of sex steroids on guinea-pig airway smooth muscle contractions. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 118:5–10.

    Article  PubMed  CAS  Google Scholar 

  37. Hellings PW, Vandekerckhove P, Claeys R, Billen J, Kasran A and Ceuppens JL (2003) Progesterone increases airway eosinophilia and hyper-responsiveness in a murine model of allergic asthma. Clin Exp Allergy 33:1457–63.

    Article  PubMed  CAS  Google Scholar 

  38. Kouloumenta V, Hatziefthimiou A, Paraskeva E, Gourgoulianis K and Molyvdas PA (2006) Non-genomic effect of testosterone on airway smooth muscle. Br J Pharmacol 149:1083–91.

    Article  PubMed  CAS  Google Scholar 

  39. Bordallo J, de Boto MJ, Meana C, Velasco L, Bordallo C, Suarez L, Cantabrana B and Sanchez M (2008) Modulatory role of endogenous androgens on airway smooth muscle tone in isolated guinea-pig and bovine trachea; involvement of beta2-adrenoceptors, the polyamine system and external calcium. Eur J Pharmacol 601:154–62.

    Article  PubMed  CAS  Google Scholar 

  40. Card JW, Carey MA, Bradbury JA, DeGraff LM, Morgan DL, Moorman MP, Flake GP and Zeldin DC (2006) Gender differences in murine airway responsiveness and lipopolysaccharide-induced inflammation. J Immunol 177:621–30.

    PubMed  CAS  Google Scholar 

  41. Stewart AG, Fernandes D and Tomlinson PR (1995) The effect of glucocorticoids on proliferation of human cultured airway smooth muscle. Br J Pharmacol 116:3219–26.

    Article  PubMed  CAS  Google Scholar 

  42. Stamatiou R, Paraskeva E, Papagianni M, Molyvdas PA and Hatziefthimiou A (2011) The mitogenic effect of testosterone and 17beta-estradiol on airway smooth muscle cells. Steroids 76:400–8. doi: S0039-128X(10)00299-0 [pii] 10.1016/j.steroids.2010.12.010

    Google Scholar 

Download references

Acknowledgments

This research was supported by the Flight Attendants Medical Research Institute (FAMRI; VS), a Small Grants Program by the Clinical Translational Science Activities (CTSA) of the Mayo Clinic (YSP), and an NIGMS T32 Institutional Training grant to the Columbia University Department of Anesthesiology (EAT).

Author information

Authors and Affiliations

  1. Departments of Physiology and Biomedical Engineering, Mayo Clinic, 4-184 W Jos SMH 200 First St SW, Rochester, MN, 55905, USA

    Y. S. Prakash M.D., Ph.D. & Venkatachalem Sathish Ph.D.

  2. Anesthesiology College of Medicine, Mayo Clinic, Rochester, MN, USA

    Y. S. Prakash M.D., Ph.D. & Venkatachalem Sathish Ph.D.

  3. Department of Anesthesiology, Columbia University, New York, NY, USA

    Elizabeth A. Townsend Ph.D.

Authors
  1. Y. S. Prakash M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Venkatachalem Sathish Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elizabeth A. Townsend Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. S. Prakash M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Albany Medical College Center for Cardiovascular Sciences, Albany, New York, USA

    Yong-Xiao Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Prakash, Y.S., Sathish, V., Townsend, E.A. (2014). Sex Steroid Signaling in the Airway. In: Wang, YX. (eds) Calcium Signaling In Airway Smooth Muscle Cells. Springer, Cham. https://doi.org/10.1007/978-3-319-01312-1_17

Download citation

Publish with us

Policies and ethics

Search

Navigation