Induced myeloperoxidase activity and related superoxide inhibition during hormone replacement therapy.

Abstract

To test whether the menopause entails any changes in the myeloperoxidase activity of neutrophil granulocytes. The effects of hormone replacement therapy on myeloperoxidase activity and related changes in free radical production were also investigated. Laboratory investigation of the effect of oestrogen on intracellular myeloperoxidase activity and release from human neutrophil granulocytes. Analysis of related changes in superoxide anion generation. 2nd Department of Medicine and 1st Department of Obstetrics and Gynaecology, Semmelweis University, Budapest. Intracellular myeloperoxidase activity (mean peroxidase index) was measured automatically in blood samples obtained for general laboratory work-up from 135 randomly selected patients in our department. Blood samples from 11 postmenopausal women were analysed before and during hormone replacement therapy. Blood samples from 20 healthy volunteers were obtained and neutrophil granulocytes separated for in vitro measurement of superoxide anion production after adding myeloperoxidase to the incubation media. The mean peroxidase index was measured using a Technicon H-3 instrument. myeloperoxidase release from neutrophils was quantified by ELISA technique. Superoxide production of isolated neutrophil granulocytes was measured by photometry. Intracellular activity of myeloperoxidase, concentration of myeloperoxidase-protein in supernatant of neutrophils, release of superoxide anion from neutrophil granulocytes. 1. Intracellular myeloperoxidase activity in neutrophils was lower in postmenopausal women, than in females with regular cycles (-1.84 +/- 3.06 versus 1.59 +/- 3.55, P < 0,001). 2. In postmenopausal women intracellular myeloperoxidase activity and myeloperoxidase release increased during hormone replacement therapy (-5.54 +/- 6.63 versus -0.2 +/- 6.05; P < 0.001 and 52.74 mU/ml +/- 25.73 versus 251.4 +/-234.1 mU/ml; P < 0.05). 3. Adding myeloperoxidase to neutrophil granulocyte suspensions, the production of superoxide anion fell (e.g. adding 280 ng/ml myeloperoxidase: 77.9 +/- 14.04 % of control production, P < 0.001). Hormone replacement restores the reduced myeloperoxidase activity in menopausal women. Adding myeloperoxidase to neutrophil granulocytes, the production of free radicals decreases.