Sexually mature virgin female rats and mice have a higher mass-specific gas-exchange surface area (Sa) and smaller alveoli than same-aged males even though mass-specific oxygen consumption (VO2) is the same, within species, in both sexes (G. D. Massaro, J. P. Mortola, and D. Massaro. Proc. Natl. Acad. Sci. USA 92: 1105-1107, 1995). We now report that rats subjected to ovariectomy at age 21 days had, at age 59 days, a smaller mass-specific Sa and larger alveoli than sham-ovariectomized rats; these differences were not due to differences in VO2 and were prevented by estrogen therapy. Furthermore, sham-ovariectomized rats treated with estrogen had smaller and more alveoli than sham-operated females not given estrogen. Androgenization of newborn female rats did not alter mass-specific Sa or alveolar size. Male mice genetically deficient in androgen receptors had the same mass-specific Sa as normal male littermates. We conclude that estrogen is responsible for the sexual dimorphism of the lung's gas-exchange region and induces the formation of smaller, more numerous alveoli in otherwise untreated female rats.
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