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Estrogen receptor regulation of pulmonary alveolar dimensions: alveolar sexual dimorphism in mice

Lung Biology Laboratory, Departments of ¹Medicine and ²Pediatrics, Georgetown University School of Medicine, Washington, District of Columbia

Submitted 24 August 2005 ; accepted in final form 15 December 2005

Female rats and mice have smaller and, per body mass (BM), more alveoli and alveolar surface area (Sa) than males of their respective species. This sexual dimorphism becomes apparent about the time of sexual maturity. It is prevented in rats (not tested in mice) by ovariectomy at age 3 wk. In female mice, estrogen receptor (ER)- and ER- are required for formation of alveoli of appropriate size and number. We now report the average volume of an alveolus (a) and the number of alveoli per body mass (Na/BM) were not statistically different between ER-^–/– and wild type (wt) males. However, the combination of a larger value for a and a smaller value for Na/BM, though neither parameter achieved a statistically significant intergroup difference, resulted in a statistically significant lower Sa/BM in ER-^–/– males compared with wt males. In ER-^–/– males, a was bigger and Na/BM and Sa/BM were lower compared with wt males. Wt males had larger alveoli and lower Na/BM and Sa/BM than wt females. The wt sexual dimorphism of a, Na/BM, and Sa/BM was absent in ER-^–/– mice. Alveolar size did not differ between ER-^–/– females and males but Na/BM and Sa/BM were greater in ER-^–/– females than in ER-^–/– males. The results in male mice, with prior findings in female mice, 1) demonstrate estrogen receptors have a smaller effect on alveolar dimensions in male than female mice, 2) show ER- and ER- are required for the sexual dimorphism of alveolar size, and 3) show ER- is needed for the sexual dimorphism of body mass-specific alveolar number and surface area.

lung function; hormone replacement therapy; chronic obstructive pulmonary disease; mutant mice

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