Induction of Calcium-Dependent Nitric Oxide Synthases by Sex Hormones

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 11; pp. 5212 - 5216
• Main Authors: Weiner, Carl P., Lizasoain, Ignacio, Baylis, Sally A., Knowles, Richard G., Charles, Ian G., Moncada, Salvador
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 24.05.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Amino Acid Oxidoreductases - biosynthesis; Amino Acid Sequence; Animal reproduction; Animals; Biochemistry; Calcium; Calcium - metabolism; Cerebellum; Complementary DNA; Enzyme Induction; Estradiol - physiology; Estrogens; Female; Gonadal Steroid Hormones - physiology; Guinea Pigs; Hormones; Kidneys; Male; Messenger RNA; Molecular Sequence Data; Nitric oxide; Nitric Oxide Synthase; Pregnancy; Progesterone - physiology; Reproduction; Rodents; Sex hormones; Skeletal muscle; Testosterone; Testosterone - physiology; Uterine artery
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.11.5212

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.