The involvement of estrogen receptors alpha and beta in the in vitro effects of 17 beta-estradiol on secretory profile of peritoneal macrophages from naturally menopausal female and middle-aged male rats

摘要

The systemic and extra- gonadal levels of 17 beta-estradiol (E2) change during aging, and affect the expression of estrogen receptors (ERs) in the immune cells of both females and males. The age-related cessation of ovarian function in females, as well as the tissue-specific expression of enzyme aromatase (estrogen synthase which significantly rises with the advancing age) in both males and females, both determine the concentration of E2 to which immune cells may be exposed. The present study was set up to investigate the direct influence of E2 in vitro on the secretory profile of peritoneal macrophages from young and naturally menopausal female rats, and from young and middle-aged male rats. The involvement of receptor(s) responsible for mediating the effects of E2 in vitro was examined by use of antagonists specific for ERa or ER beta. Whereas in macrophages from young female rats E2 treatment diminished interleukin (IL)-1 beta secretion, it increased it in young males, and the middleaged females. The in vitro E2 treatment increased tumor necrosis factor (TNF)-alpha release by macrophages from young rats of both sexes, while it increased macrophage IL-6 release independently of both sex and age. At the same time, E2 decreased hydrogen peroxide (H2O2) production in macrophages from females, and increased it in male rats of both ages, whereas it diminished nitric oxide (NO) release in all experimental groups. Inspite of the sex-and age-specific effects of E2 on macrophage urea release, E2 did not affect the NO/urea ratio in macrophages from female rats, and diminished it in macrophages from both young and middle-aged male rats. Independently of the sex and age, E2 stimulated the release of inflammatory cytokines predominantly via macrophage ER alpha, and inhibited the IL-1 beta release in young females via ER beta. In contrast, E2 increased macrophage H2O2 and urea production by activating ER beta, but diminished their release via ER alpha. Our study may contribute to better understanding of the complex role(s) that E2 may play in innate immunity during aging, and that are dependent of sex.