INDUCTION OF CALCIUM-DEPENDENT NITRIC-OXIDE SYNTHASES BY SEX-HORMONES

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 ac tivity of calcium-dependent NOS in the uterine artery and at least a d oubling in the heart, kidney, skeletal muscle, esophagus, and cerebell um. The increase in NOS activity in the cerebellum during pregnancy wa s inhibited by the estrogen-receptor antagonist tamoxifen. Treatment w ith estradiol (but not progesterone) also increased calcium-dependent NOS activity in the tissues examined from both females and males. Test osterone increased calcium-dependent NOS only in the cerebellum. No si gnificant change in calcium-independent NOS activity was observed eith er during pregnancy or after the administration of any sex hormone. Bo th pregnancy and estradiol treatment increased the amount of mRNAs for NOS isozymes eNOS and nNOS in skeletal muscle, suggesting that the in creases in NOS activity result from enzyme induction. Thus both eNOS a nd nNOS are subject to regulation by estrogen, an action that could ex plain some of the changes that occur during pregnancy and some gender differences in physiology and pathophysiology.