DIHYDROTESTOSTERONE INHIBITS FETAL RABBIT PULMONARY SURFACTANT PRODUCTION
DIHYDROTESTOSTERONE INHIBITS FETAL RABBIT PULMONARY SURFACTANT PRODUCTION
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DOI：
10.1172/jci110488
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发表时间：
1982-01-01
影响因子：
15.9
通讯作者：
TORDAY, JS
中科院分区：
文献类型：
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作者：
NIELSEN, HC;ZINMAN, HM;TORDAY, JS
人类新生儿男性比女性有更高的新生儿呼吸窘迫综合征（RDS）的发病率和死亡率，并且对旨在通过刺激胎儿肺表面活性物质产生来预防RDS的激素治疗的反应较差。雄性胎儿表现出延迟产生肺表面活性物质。为了确定胎兔肺表面活性物质产生的性别差异是否受激素控制，在妊娠26天胎兔肺灌洗液中测量肺表面活性物质的饱和磷脂酰胆碱/鞘磷脂比（SPC/S）。相邻胎儿的性别与女性胎儿的SPC/S比值之间存在相关性，例如，与1或2个男性相邻，女性胎儿的SPC/S比值降低（P < 0.05）。妊娠12 ~ 26 d的母兔分别注射0.1、1.0、10和25 mg/d的双氢睾酮（DHT），于26 d测定胎肺灌洗液中SPC/S比值。在胎儿血清雄激素水平具有正常性别差异的组（对照组，0.1 mg DHT/d）中，SPC/S比值也存在正常性别差异（女性>男性，P = 0.03）。在1 mg/d组中，雄激素水平无性别差异，SPC/S比值的性别差异也被消除，因为雌性值降低至雄性水平。较高剂量的DHT（10，25 mg/d）进一步降低SPC/S比值。从妊娠第12-26天开始注射抗雄激素Fluoride（25 mg/d）。该处理通过增加雄性动物与雌性动物的比率，消除了肺灌洗液SPC/S比率的正常性别差异。显然，雄激素抑制胎儿肺表面活性物质的产生。了解表面活性物质产生的性别差异机制可能有助于开发对男性和女性同样有效的预防RDS的治疗方法。
Human neonatal males have a higher morbidity and mortality for neonatal respiratory distress syndrome (RDS) than females, and respond less well to hormone therapy designed to prevent RDS by stimulating fetal pulmonary surfactant production. Male fetuses exhibit delayed production of pulmonary surfactant. To determine if the sex difference in fetal pulmonary surfactant production is under hormonal control, pulmonary surfactant was measured as the saturated phosphatidylcholine/sphingomyelin ratio (SPC/S) in the lung lavage of fetal rabbits at 26 d [day] gestation. There was an association between the sex of neighboring fetuses and the SPC/S ratio of the female fetuses, such that with 1 or 2 male neighbors, females had decreasing SPC/S ratios (P < 0.05). Dihydrotestosterone (DHT) was injected into pregnant does from day 12 through 26 of gestation in doses of 0.1, 1.0, 10 and 25 mg/d and the SPC/S ratio in fetal lung lavage was measured on day 26. In groups with the normal sex difference in fetal serum androgen levels (controls, 0.1 mg DHT/d), the normal sex difference in the SPC/S ratio was also present (females > males, P = 0.03). In the 1-mg/d group there was no sex difference in androgen levels and the sex difference in the SPC/S ratio was also eliminated as the female values were lowered to the male level. Higher doses of DHT (10, 25 mg/d) further reduced the SPC/S ratios. The anti-androgen Flutamide (25 mg/d) was injected from day 12-26 of gestation. This treatment eliminated the normal sex difference in the lung lavage SPC/S ratio by increasing the male ratios to that of the females. Evidently, androgens inhibit fetal pulmonary surfactant production. An understanding of the mechanism of the sex difference in surfactant production may allow development of therapy that is as effective in males as in females for preventing RDS.