INDUCTION OF INDUCIBLE NITRIC-OXIDE SYNTHASE EXPRESSION IN HUMAN SECRETORY ENDOMETRIUM

The endometrial secretory phase is characterized by stromal oedema, a premenstrual increase in stromal macrophages and an increased cytokine production as menstruation approaches, Nitric oxide (NO) is a mediato r of vasodilatation and cytotoxicity which is synthesized from L-argin ine by NO synthases (NOS), These enzymes are either constitutively exp ressed or induced by lipopolysaccharides and/or cytokines, The presenc e and function of the inducible isoform of NOS (iNOS) in normal human endometrium has not been fully elucidated until recently, Frozen tissu e sections taken from 22 women who underwent hysterectomy and adnexect omy for benign disease were immunostained with antibodies raised again st the different NOS isoforms to investigate the presence of NOS in hu man endometrium, iNOS stained positive in the glandular epithelial cel ls of the secretory endometrium, Staining was either weak or absent in the proliferative and inactive endometrium, as well as in the oviduct and the glandular epithelium of the endocervix. The stroma remained u niformly negative, Immunoreactivity for endothelial constitutive NOS ( eNOS) was confined exclusively to endothelial cells, Furthermore, epit helial cells from endometrium, oviduct and endocervix and all endothel ial cells showed positive staining for reduced nicotinamide adenine di nucleotide phosphate (NADPH)-diaphorase, which is a histochemical mark er for NOS activity. Reverse transcriptase polymerase chain reaction ( RT-PCR) was performed in order to assess the presence of NOS mRNA. Abu ndant expression of iNOS mRNA was detected in the secretory phase endo metrium only, The strong expression of inducible NO synthase in human secretory phase endometrium suggests that the increased production of NO, probably induced by cytokines, may be relevant to the process of m enstruation.