Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice
Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice
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DOI：
10.1152/ajplung.00228.2004
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发表时间：
2004-12-01
影响因子：
4.9
通讯作者：
Massaro, GD
中科院分区：
文献类型：
--
作者：
Massaro, D;Massaro, GD
肺组织弹性回缩力以及肺气体交换单位（肺泡）的尺寸和数量是气体交换功能的主要决定因素。健康老年人在绝经后气体交换功能的丧失会加速，而患有慢性阻塞性肺病（COPD）的个体则逐渐丧失。后者是一种中年及以后的疾病，虽然在男性中比在女性中更常见，但女性吸烟者和从不吸烟者可能比男性更容易患这种疾病；其特征是肺组织弹性回缩力减弱和目前无法补救的肺泡损失。性成熟大鼠的卵巢切除会减少肺泡的形成，而雌激素可以防止这种减少。在目前的工作中，我们发现雌激素受体-α和雌激素受体-β是唯一公认的哺乳动物雌激素受体，是雌性小鼠形成完整肺泡所必需的。然而，只有雌激素受体-β 的缺失才会减少肺弹性组织的反冲力。此外，成年小鼠的卵巢切除术在3周内导致肺泡和肺泡表面积的损失，但肺容量没有变化。肺泡丢失后，雌激素替代可诱导肺泡再生，逆转卵巢切除术的结构效应。这些研究 1) 揭示雌激素受体以非冗余的方式调节肺泡大小和数量，2) 表明雌激素是维持已形成的肺泡所必需的，并在成年卵巢切除小鼠中诱导肺泡再生，3) 提供了雌激素可以减缓慢性阻塞性肺病女性肺泡损失并诱导肺泡再生的可能性。
Lung tissue elastic recoil and the dimension and number of pulmonary gas-exchange units ( alveoli) are major determinants of gas-exchange function. Loss of gas-exchange function accelerates after menopause in the healthy aged and is progressively lost in individuals with chronic obstructive pulmonary disease ( COPD). The latter, a disease of midlife and later, though more common in men than in women, is a disease to which women smokers and never smokers may be more susceptible than men; it is characterized by diminished lung tissue elastic recoil and presently irremediable alveolar loss. Ovariectomy in sexually immature rats diminishes the formation of alveoli, and estrogen prevents the diminution. In the present work, we found that estrogen receptor-alpha and estrogen receptor-beta, the only recognized mammalian estrogen receptors, are required for the formation of a full complement of alveoli in female mice. However, only the absence of estrogen receptor-beta diminishes lung elastic tissue recoil. Furthermore, ovariectomy in adult mice results, within 3 wk, in loss of alveoli and of alveolar surface area without a change of lung volume. Estrogen replacement, after alveolar loss, induces alveolar regeneration, reversing the architectural effects of ovariectomy. These studies 1) reveal estrogen receptors regulate alveolar size and number in a nonredundant manner, 2) show estrogen is required for maintenance of already formed alveoli and induces alveolar regeneration after their loss in adult ovariectomized mice, and 3) offer the possibility estrogen can slow alveolar loss and induce alveolar regeneration in women with COPD.