Nitric oxide synthase in female reproductive and urinary organs: Hormonal regulation and functional significance

Abstract: Nitric oxide synthase (NOS) activity was studied in cytosolic and particulate fractions in reproductive organs from rabbit (uterus and vagina) and rat (uterus, vagina and cervix). NOS was found predominantly in cytosolic fractions in all tissues and the activity of NOS in both fractions was highly Ca2+ dependent. NOS activity in vagina and cervix were much higher (3-6-fold) than in the uterus. Estrogen (E2) downregulated NOS in all tissues except in cerebellum (rabbit) or cerebral cortex (rat) used as non-target (reference) for E2. A downregulation by E2 of NOS activity in rabbit lower urinary tract, but not in the upper urinary tract was also found. These data in hormone treated animals led us to conclude a) that NO production is regulated by ovarian steroids, particularly by E2 in uterus and vagina, and suggests a physiological significance b) an upregulation by progesterone (P) of vaginal NOS and NO dependent response of vaginal smooth muscle suggests a tissue specific role. Studies were also performed on human tissues. Trophoblast was taken from abortions, placenta and myometrium from Cesarean deliveries at term. NOS activity was found in both cytosolic and particulate fractions of all tissues. NOS activity, as in the tissues from rat and rabbit, was highly Ca2+ dependent but in contrast to tissues from rat and rabbit the NOS in human tissues was predominantly found in the particulate fraction, suggesting eNOS. Compared to trophoblast or placenta NOS activity in the myometrium was marginal. The data suggest that NO produced by the trophoblast which was relatively high in both villous and extravillous trophoblast may substantially contribute to maintenance of uterine quiescence through a paracrine effect during early pregnancy. Similar paracrine action of placental NOS which was 2-4-fold higher than the myometrium could be envisioned during late pregnancy.

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