INDUCTION OF CALCIUM-DEPENDENT NITRIC-OXIDE SYNTHASES BY SEX-HORMONES
INDUCTION OF CALCIUM-DEPENDENT NITRIC-OXIDE SYNTHASES BY SEX-HORMONES
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DOI：
10.1073/pnas.91.11.5212
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发表时间：
1994-05-24
影响因子：
11.1
通讯作者：
MONCADA, S
中科院分区：
文献类型：
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作者：
WEINER, CP;LIZASOAIN, I;MONCADA, S
我们研究了妊娠和性激素对豚鼠钙依赖性和非钙依赖性一氧化氮合酶（NOS）的影响。妊娠（近期）导致子宫动脉中钙依赖性NOS活性增加>4倍，心脏、肾脏、骨骼肌、食管和小脑中至少增加一倍。雌激素受体拮抗剂他莫昔芬可抑制妊娠期间小脑NOS活性的增加。雌二醇（而不是孕酮）治疗也增加了钙依赖性NOS活性的组织检查从女性和男性。替吉奥仅在小脑中增加钙依赖性NOS。无论是在怀孕期间或任何性激素的管理后，钙非依赖性NOS活性没有显着变化。妊娠和雌二醇治疗增加了骨骼肌中NOS同工酶eNOS和nNOS的mRNA量，表明NOS活性的增加是由酶诱导引起的。因此，eNOS和nNOS都受到雌激素的调节，这一作用可以解释怀孕期间发生的一些变化以及生理学和病理生理学上的一些性别差异。
We have examined the effects of pregnancy and sex hormones on calcium-dependent and calcium-independent nitric oxide synthases (NOSs) in the guinea pig. Pregnancy (near term) caused a >4-fold increase in the activity of calcium-dependent NOS in the uterine artery and at least a doubling in the heart, kidney, skeletal muscle, esophagus, and cerebellum. The increase in NOS activity in the cerebellum during pregnancy was inhibited by the estrogen-receptor antagonist tamoxifen. Treatment with estradiol (but not progesterone) also increased calcium-dependent NOS activity in the tissues examined from both females and males. Testosterone increased calcium-dependent NOS only in the cerebellum. No significant change in calcium-independent NOS activity was observed either during pregnancy or after the administration of any sex hormone. Both pregnancy and estradiol treatment increased the amount of mRNAs for NOS isozymes eNOS and nNOS in skeletal muscle, suggesting that the increases in NOS activity result from enzyme induction. Thus both eNOS and nNOS are subject to regulation by estrogen, an action that could explain some of the changes that occur during pregnancy and some gender differences in physiology and pathophysiology.