Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer.

The active vitamin D hormone, 1,25-dihydroxyvitamin D , exerts many physiological actions in the body, including effects on the nervous system. Studies of steroidogenesis in cells of the nervous system and elsewhere not only indicate that 1,25-dihydroxyvitamin D affects steroidogenic pathways but also suggest varying responses in different cell types. For example, 1,25-dihydroxyvitamin D stimulates the expression of aromatase in human glioma but not in human neuroblastoma cells or rat astrocytes. However, in astrocytes, 1,25-dihydroxyvitamin D suppresses 3β-hydroxysteroid dehydrogenase and steroid 17-hydroxylase/lyase. Other studies indicate cross-talk between vitamin D signalling and signalling of oestrogens, progesterone or glucocorticoids. Reported data indicate synergistic effects of combinations of 1,25-dihydroxyvitamin D and other steroid hormones on neuroinflammation, neurite outgrowth and neuroprotection. Also, dysregulation of steroid pathways affecting brain cells is found in vitamin D deficiency. Thus, several studies suggest that active vitamin D may affect steroid hormone synthesis and/or signalling in the nervous system, although the potential mechanisms for these responses remain unclear. 1,25-Dihydroxyvitamin D suppresses proliferation in several cell types and is therefore of interest in cancer treatment. Also, epidemiological studies associate vitamin D levels with cancer risk or outcomes. Reported data on tumours of the nervous system are mainly on glioma, a common type of brain cancer. Expression of the vitamin D receptor in glioma tumours is associated with improved survival. Several studies show that 1,25-dihydroxyvitamin D and vitamin D analogues (synthetic vitamin D-like compounds) suppress proliferation and migration in human vitamin D receptor-expressing glioma cell lines. Studies on mechanisms for actions of 1,25-dihydroxyvitamin D or its analogues indicate regulation of cell cycle proteins and senescence markers. These compounds also show synergism in combination with other cancer therapies treating glioma. From the data available, vitamin D analogues emerge as interesting candidates for the future improved treatment of human glioma and possibly also other cancers of the nervous system.