In 2007 we demonstrated that SHBG is taken up into brain cells in vivo (see picture above taken from the Neuroendocrinology 86:84-93 paper) and that mouse fetal hippocampal HT22 cells also take up SHBG if they have been stably transfected with cDNA for estradiol receptor-beta (ERβ) but if they had ERα, suggesting a specific link between ERβ and whatever mechanism is responsible for SHBG internalization into brain cells (SHBG receptor?). We are now trying to follow up this work using fluorimetric methods.

Dr. Zsofi Herbert did some excellent work in my laboratory and went back to Germany to work with my colleague Dr. Gustav Jirikowski doing many things including SELDI-TOF mass spectrometry for SHBG in brain and neurohypophysis (NHP in picture above). That estradiol (E2 in figure) eliminated SHBG from the posterior pituitary, a release- but not production-site for SHBG, indicated that steroids may act rapidly to induce the release of SHBG. We are now following up on this finding by examining the same HT22 cells above for the release of SHBG in response to steroids.

We have demonstrated CBG in the brain (Mopert et al. Hormones and Metabolic Research 38:246-252, 2006), in many of the same areas as SHBG, and have more recently discovered it in the nose; more specifically in the nasal epithelium and particularly in the vomeronasal organ (see picture above, yellow arrows indicate CBG in outer edge of vomeronasal mucosa; from work by Dr. Wilfred Doelz). It remains to be determined what CBG or SHBG, which is also found in the olfactory system, are doing in the nose. We have postulated that they are capturing aerosol steroids.

The picture above is an amazing freeze-fracture technique that allows EM visualization of the inner and outer surfaces of cells. In this case the cell has CBG on the outer side of the cell membrane just adjacent to a caveola, suggesting that CBG is associated with this important steroid uptake area. This work, done by Dr. Jirikowski, is at the leading edge of immunochemical techniques.