Membrane estrogen and glucocorticoid receptors--implications for hormonal control of immune function and autoimmunity

Membrane steroid receptors (mSRs) have recently re-emerged as candidates for mediating steroid effects which do not fit the paradigm of nuclear transcription factor mechanisms. We have studied two steroid-binding classes of mSRs, and have noted striking similarities in their characteristics (immunocytochemical appearance, biochemical properties, proteolytic sensitivity, signaling pathways, regulation, and molecular origins). These observations strengthen the conclusion that mSRs can be modified versions of intracellular steroid receptors. The membrane estrogen receptors (mERs) we studied are involved in estrogen-induced release of prolactin. Membrane glucocorticoid receptors (mGRs) in both mouse and human lymphoma cells are necessary for the initiation of glucocorticoid-induced therapeutic apoptosis which is related to the developmental phenomenon of thymic involution. Diseases of autoimmunity such as systemic lupus erythematosus and arthritis are related to estrogen status. Since both of these mSRs have recently been found in both normal and cancerous lymphoid cells, actions of these mSRs may have important consequences for functions and diseases of the immune system. Therefore, the study of these forms of steroid receptors may present novel therapeutic opportunities for the use of steroids and steroid analogs.