Steroidal pheromones and their potential target sites in the vomeronasal organ.

Steroids are important olfactory signals in most mammalian species. The vomeronasal organ has been suspected to be the primary target of pheromones. In rat vomeronasal sensory neurons express steroid binding proteins and nuclear receptors. Some binding globulins were found also in single ciliated cells of the non-sensory vomeronasal epithelium. Immunoelectron microscopy revealed VDR in olfactory microvilli and DPB in apical membrane protrusions of supporting sells within the sensory epithelium. Pilot behavioral studies with dogs showed increased sniffing duration upon exposure to low concentrations of vitamin D while higher concentrations were less effective. It has been shown that vitamin D has pheromone-like properties in lizards. Our histochemical and behavioral observations indicate that the mammalian vomeronasal organ may be a vitamin D target. Olfactory functions of vitamin D involve most likely rapid membrane mediated effects rather than actions through nuclear receptors.

Evidence for accessory chemosensory cells in the adult human nasal cavity.

The existence of functionally relevant accessory olfactory organs in humans is still a matter of controversy. A vomeronasal organ (VNO) with sensory and non-sensory epithelia exists only in macrosmatic mammals. A similar structure is regularly observed in humans during fetal development. The postnatal persistence of a VNO like epithelial duct has been described in about 10 %. Here we studied tissue samples of nasal mucosa from adults. In all individuals we found epithelial cells in the lower part of the nasal septum which exhibited morphological features of sensory neurons and which showed immunostaining for olfactory marker protein OMP. These cells were interposed by ciliated cells, goblet cells and small intraepithelial capillaries. Only occasionally we found such cells within a morphologically defined epithelial duct. A clear separation of sensory and non-sensory epithelia could not be observed. In most cases we found OMP positive groups of cells either in epithelial cavities or just embedded in respiratory epithelium. With RT-PCR we could confirm the presence of OMP encoding mRNA thus supporting the idea of intrinsic expression of this protein in the nasal mucosa. We conclude that accessory chemosensory structures are regularly conserved in adult humans in the approximate anatomical location of the VNO of microsmatic animals. Their functional importance is yet to be determined.

Estrogen receptors and sex hormone binding globulin in neuronal cells and tissue.

Estrogens exert a critical influence on neuronal tissues and cells. As demonstrated in many clinical studies, estrogens are neuroprotective to the extent that they improve prognosis for women with neurodegenerative diseases. Unfortunately, we still do not know exactly how these effects are mediated. Fifty years ago the first estrogen receptor was found, but since then many other new pathways of estrogen action have been identified. This review describes several of these pathways of estrogen effects and provides some conclusions and correlations about these as determined by recent studies with nerve growth factor differentiated rat pheochromocytoma cell line.

Antagonizing effects of membrane-acting androgens on the eicosanoid receptor OXER1 in prostate cancer.

Accumulating evidence during the last decades revealed that androgen can exert membrane initiated actions that involve signaling via specific kinases and the modulation of significant cellular processes, important for prostate cancer cell growth and metastasis. Results of the present work clearly show that androgens can specifically act at the membrane level via the GPCR oxoeicosanoid receptor 1 (OXER1) in prostate cancer cells. In fact, OXER1 expression parallels that of membrane androgen binding in prostate cancer cell lines and tumor specimens, while in silico docking simulation of OXER1 showed that testosterone could bind to OXER1 within the same grove as 5-OxoETE, the natural ligand of OXER1. Interestingly, testosterone antagonizes the effects of 5-oxoETE on specific signaling pathways and rapid effects such as actin cytoskeleton reorganization that ultimately can modulate cell migration and metastasis. These findings verify that membrane-acting androgens exert specific effects through an antagonistic interaction with OXER1. Additionally, this interaction between androgen and OXER1, which is an arachidonic acid metabolite receptor expressed in prostate cancer, provides a novel link between steroid and lipid actions and renders OXER1 as new player in the disease. These findings should be taken into account in the design of novel therapeutic approaches in prostate cancer.

Actual Isothermal Effects of Water-Filtered Infrared A-Irradiation.

In this study, the athermal effects of water-filtered infrared A (wIRA)-irradiation (780-1400 nm) on human dermal fibroblasts were investigated. For this purpose, cells were exposed to wIRA-irradiation (178 mW cm(-2) for 1 h), while a sophisticated experimental setup prevented warming of the samples exceeding 0.1°C. The investigated parameters were the formation of reactive oxygen species (ROS), mitochondrial membrane potential and superoxide release, protein oxidation, proliferation rate, as well as intracellular Ca(2+) -release in single cells, most of them quantified via fluorescence microscopy and fluorimetric techniques. The existence of actual athermal wIRA-effects is still intensively discussed, since their detection requires a careful experimental setup and both efficient and powerful temperature regulation of the exposed samples. Here, we can definitively show that some of the supposed athermal wIRA-effects may be rather artifacts, since wIRA did not reveal any impact on the above mentioned parameters-as long as the temperature of the exposed cells was carefully maintained. Though, we were able to identify an athermal DNA-protective wIRA-effect, since the induced DNA damage (quantified via 8-Oxo-G-formation) was significantly decreased after a subsequent UVB-exposure. These results suggest that many of the supposed athermal wIRA-effects can be induced by pure warming of the samples, independent from any wIRA-irradiation.

Estrogen dependent expression of sex hormone binding globulin in PC 12 cells.

Rat pheochromocytoma PC 12 cells are known to develop features of dopaminergic neurons upon treatment with nerve growth factor. They express in part estrogen receptors α and ß, and G-protein coupled receptor 30. Estrogens promote development of these cells and exert neuroprotective effects. Here we treated differentiated PC 12 cells with physiological concentrations of 17-ß-estradiol. We observed with immunocytochemistry cytoplasmic staining for SHBG in a portion of these cells Double immunostaining for estrogen receptor-ß revealed that some PC 12 cells contained both antigens. Numbers of estrogen receptor-ß positive cells were significantly higher after estradiol treatment; an effect that was not altered by pretreatment of cultures with tamoxifen. With reverse transcriptase polymerase chain reaction we observed sex hormone binding globulin encoding transcripts indicating intrinsic expression of the steroid binding globulin. We conclude that estrogen treatment induces SHBG expression in differentiated PC12.