Sex hormone-dependent regulation of cilia beat frequency in airway epithelium

Raksha Jain, Jennifer M. Ray, Jie Hong Pan, Steven L. Brody

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Previous studies have demonstrated a female disadvantage in airway diseases, such as asthma and bronchiectasis. The basis for this sex disparity is unknown. We hypothesized that the female sex hormone, progesterone (P4), inhibits functions of the normal airway mucociliary apparatus. P4 receptor (PR) expression was evaluated in human lung and cultured primary human airway epithelial cells isolated from male and female lung transplant donors. PR expression was restricted to the proximal region of the cilia of airway epithelia, and was similar in men and women. Expression of isoform PR-B was more abundant than PR-A in cells from both sexes. Airway epithelial cell exposure to P4 decreased cilia beat frequency (CBF) by 42.3% (±7.2). Inhibition of CBF was prevented by coadministration of P4 with the active form of estrogen, 17β-estradiol, or the PR antagonist, mifepristone. P4 inhibition was time and dose dependent, with a significant decrease by 8 hours and maximal effect at 24 hours, accompanied by translocation of PR from the cilia to the nucleus. Inhibition of cilia beat was also prevented by treatment of cells with actinomycin D, suggesting that CBF inhibition is a transcriptionally mediated event. Together, these findings indicate that sex hormones influence the function of a key component of the mucociliary apparatus. These mechanisms may contribute to the sex disparity present in airway diseases and provide therapeutic targets for the treatment of these debilitating airway diseases.

Original languageEnglish (US)
Pages (from-to)446-453
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume46
Issue number4
DOIs
StatePublished - Apr 2012

Fingerprint

Cilia
Gonadal Steroid Hormones
Epithelium
Epithelial Cells
Mifepristone
Lung
Bronchiectasis
Dactinomycin
Transplants
Progesterone
Estradiol
Protein Isoforms
Estrogens
Therapeutics
Asthma
Tissue Donors
Cells

Keywords

  • Cilia
  • Cilia beat frequency
  • Lung disease
  • Progesterone receptor
  • Sex disparity

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Sex hormone-dependent regulation of cilia beat frequency in airway epithelium. / Jain, Raksha; Ray, Jennifer M.; Pan, Jie Hong; Brody, Steven L.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 46, No. 4, 04.2012, p. 446-453.

Research output: Contribution to journalArticle

Jain, Raksha ; Ray, Jennifer M. ; Pan, Jie Hong ; Brody, Steven L. / Sex hormone-dependent regulation of cilia beat frequency in airway epithelium. In: American Journal of Respiratory Cell and Molecular Biology. 2012 ; Vol. 46, No. 4. pp. 446-453.
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