Sex hormone binding globulin and corticosteroid binding globulin as major effectors of steroid action

•SHBG and CBG are expressed in various organs including liver, adrenals, pituitary, and brain.•Steroid binding globulins can be incorporated and accumulated by various cell types.•Fluorescent steroids can be used to monitor cellular internalization.•Treating cells with SHBG antibody blocks this steroid uptake.•Steroid binding globulins may have specific membrane receptors.

Contrary to the long-held postulate of steroid-hormone binding globulin action, these protein carriers of steroids are major players in steroid actions in the body. This manuscript will focus on our work with sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) and demonstrate how they are actively involved in the uptake, intracellular transport, and possibly release of steroids from cells. This manuscript will also discuss our own findings that the steroid estradiol is taken up into the cell, as demonstrated by uptake of fluorescence labeled estradiol into Chinese hamster ovary (CHO) cells, and into the cytoplasm where it may have multiple actions that do not seem to involve the cell nucleus. This manuscript will focus mainly on events in two compartments of the cell, the plasma membrane and the cytoplasm.