Three steroid-binding globulins, their localization in the brain and nose, and what they might be doing there.

Steroid-binding globulins (SBGs) such as sex hormone binding globulin, corticosteroid binding globulin, and vitamin-D binding protein are receiving increasing notice as being actively involved in steroid actions. This paper reviews data of all three of these SBGs, focusing on their presence and possible activity in the brain and nose. We have found all three proteins in the brain in limbic areas such as the paraventricular (PVN) and supraoptic nuclei (SON) as well as other areas of the hypothalamus, hippocampus, and medial preoptic area. There is also evidence that all three are made in the PVN and SON, in conjunction with the neuropeptides oxytocin and vasopressin. The localization of these three SBGs is more variable within areas of the main olfactory area and the vomeronasal organ. However, all three are found in the mucus of these areas, suggesting that one of their functions is to sequester aerosol steroids, such as pheromones, and deliver them to sensory cells and then to deeper sensory areas. In this manuscript, we present multiple models of SBG action including: A) SBG binding to a membrane receptor, B) this SBG receptor being associated with a larger protein complex including cytoplasmic steroid receptors, C) when the SBGs binds to their SBG receptors, second messengers within the cells respond, D) after SBG binding to its receptor, it releases its associated steroid into the membrane's lipid bilayer, from which it gains access into the cell only when bound by an internal protein, E) the SBG, possibly with its bound SBG receptor, is internalized into the cell from which it can gain access to numerous organelles and possibly the cell's nucleus or F) associate with intracellular steroid receptors, G) SBGs produced in target cells are released from those cells upon specific stimulation, and H) according to the Free Steroid Hypothesis steroids released from the extracellular SBG passively diffuse across the plasma membrane of the cell. These models move the area of steroid endocrinology forward by providing important paths of steroid activity within many steroid target cells.