Elevation of inducible nitric oxide synthase activity in human endometriumduring menstruation

Nitric oxide (NO) is a known agonist of programmed cell death (apoptosis). In order to discover its potential role during menstrual shedding, a proces s associated with extensive apoptosis, we evaluated activity and mRNA level s of the inducible and constitutive isoforms of NO synthase (NOS) in endome trial specimens of the proliferative (n = 11), late-secretory (n = 7), and menstrual (n = 17) phase of the cycle. These levels were compared with the proportion of apoptotic cells by detection of histochemically labeled DNA f ragments. Inducible NOS (iNOS) activity during menstruation was six times t hat of the proliferative or late-secretory phase (p < 0.05), whereas consti tutive NOS activity remained unchanged. Competitive reverse transcription-p olymerase chain reaction revealed 146% and 77% increases of iNOS mRNA expre ssion in the late-secretory and menstrual phases, respectively, compared to the proliferative phase (p < 0.05), whereas constitutive NOS mRNA expressi on remained constant. Inducible NOS immunostaining was restricted to epithe lial cells, whereas constitutive NOS immunostaining was confined to vascula r endothelia. In addition, the proportion of apoptotic cells within the gla nds of late-secretory or menstrual endometrium was twice that of the prolif erative phase (p < 0.05). We conclude that local production of NO is involved in the signal transduct ion mechanisms leading to endometrial breakdown during menstruation.