Modulation of TNF alpha and nitric oxide production by macrophages and uterine protein expression in mice chronically treated with sex steroids

The objective of the current studies was to analyze the relation of sex ste roid treatment with the pattern of uterine secretory proteins and productio n of tumor necrosis factor alpha (TNF alpha) and nitric oxide (NO) by murin e macrophages. Specific pathogen free (SPF) CDI mice were ovariectomized an d divided into 6 groups which were treated with different sex steroids: pro gesterone (group 2), estradiole (group 3), progesterone plus estradiole (gr oup 4), estradiole plus progesterone (group 5), testosterone (group 6) and placebo (group 1). The treatments were continued by subcutaneous embedding of hormone pellets for 30 days. Total white blood cell counts in groups 4 a nd 5 showed a statistically higher total leukocyte count (p less than or eq ual to 0.05) than that in groups 2 and 6 (p less than or equal to 0.05). Li popolysaccharide (LPS)-stimulated peritoneal macrophages from estrogen-trea ted mice produced a significantly higher level of NO than those in the othe r groups (p less than or equal to 0.05). TNF alpha production by the macrop hages significantly increased by estrogen or testosterone treatment compare d with the control (p less than or equal to 0.05). LPS induced a 2 fold pro duction of both TNF alpha and NO by peritoneal macrophages. It was observed that steroid treatment induced a de Move synthesis of products with patter ns specific to uterine proteins. Our results showed that sex steroids affec t the macrophage function and modulate the pattern of secretory uterine pro teins. The usefulness of the mouse model with subcutaneous embedding of hor mone was also demonstrated.