Nuclear factor-kappa-B/steroid hormone receptor interactions as a functional basis of anti-inflammatory action of steroids in reproductive organs.

The transcription factor, nuclear factor-kappa-B (NF-kappa B), can be induced by pro-inflammatory cytokines and is important in immunological and inflammatory processes because it directs transcription of chemoattractants, cytokines (including the NF-kappa B-inducing cytokines themselves), cytokine receptors and cell adhesion molecules. We and others have recently found that NF-kappa B and the glucocorticoid or progesterone receptor mutually suppress each other's activity. Because of its central role in signal transduction in immunological and inflammatory responses, inhibition of NF-kappa B activity by glucocorticoids and progestins provides an explanation for the anti-inflammatory and immunosuppressive activity of these molecules. Since suppression of inflammatory processes leading to menstruation and parturition are among the key functions of progesterone, the repression of NF-kappa B activity by the progesterone receptor may prove to be essential in the regulation of these processes. Recent data show that it may be possible to select progesterone receptor ligands that are more efficient suppressors of NF-kappa B activity, and which may therefore be more effective in modulating these major reproductive processes.