Testosterone deficiency promotes the development of pulmonary emphysema in orchiectomized mice exposed to elastase

Biochem Biophys Res Commun. 2021 Jun 18:558:94-101. doi: 10.1016/j.bbrc.2021.04.051. Epub 2021 Apr 24.

Abstract

Testosterone deficiency is commonly observed in male patients with chronic obstructive pulmonary disease (COPD), which is characterized by chronic inflammation of the airways and pulmonary emphysema. Although clinical trials have indicated that testosterone replacement therapy can improve respiratory function in patients with COPD, the role of testosterone in the pathogenesis of COPD remains unclear. The aim of this study was to explore the effect of testosterone deficiency on the development of pulmonary emphysema in orchiectomized (ORX) mice exposed to porcine pancreatic elastase (PPE). ORX mice developed more severe emphysematous changes 21 d after PPE inhalation than non-ORX mice. Testosterone propionate supplementation significantly reduced PPE-induced emphysematous changes in ORX mice. PPE exposure also increased the number of neutrophils and T cells in bronchoalveolar lavage fluid (BALF) of mice that had undergone ORX and sham surgery. T cell counts were significantly higher in the BALF of ORX mice than of sham mice. Testosterone supplementation reduced the infiltration of T cells into BALF and alleviated emphysematous changes in the lungs of ORX mice. Our findings suggest that testosterone, a male-specific hormone, may suppress the development of pulmonary emphysema through the regulation of T cell-mediated immunity.

Keywords: COPD; Chronic obstructive pulmonary disease; Emphysema; Testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal
  • Humans
  • Immunity, Cellular / drug effects
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Orchiectomy
  • Pancreatic Elastase / administration & dosage
  • Pancreatic Elastase / toxicity
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Emphysema / etiology*
  • Pulmonary Emphysema / immunology
  • Pulmonary Emphysema / pathology
  • Swine
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Testosterone / administration & dosage
  • Testosterone / deficiency*

Substances

  • Testosterone
  • Pancreatic Elastase