Induction of calcium-dependent nitric oxide synthases by sex hormones.

TLDR

The study investigated how pregnancy and sex hormones influence calcium‑dependent and calcium‑independent nitric oxide synthases in guinea pigs. The authors measured NOS activity and mRNA expression in multiple tissues of guinea pigs during pregnancy and after hormone administration. Pregnancy and estradiol markedly increased calcium‑dependent NOS activity (over four‑fold in uterine artery and doubled in heart, kidney, skeletal muscle, esophagus, cerebellum) and upregulated eNOS/nNOS mRNA in skeletal muscle, while testosterone only affected cerebellar NOS; calcium‑independent NOS remained unchanged, and the cerebellar response was blocked by tamoxifen, indicating estrogen‑mediated regulation of eNOS and nNOS.

Abstract

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.