VITAMINS

Retmoid is defined as biological isosters of vitamin A acid (all-trans-retmoic acid, ATRA), and acts as internal hormone that regulates a number of biological functions, such as cell differentiation, proliferation and embryonic development in vertebrates. The pleiotropic activities of retinoids are mediated by binding to and activating two classes of nuclear receptors, retinoic acid receptors (RAR α, β, γ) and retmoid X receptors (RXR α, β, γ), both of which belong to the steroid/thyroid hormone nuclear receptor superfamily, and are hgand-mducible transcription factors. We have designed and synthesized several kinds of novel RAR- or RXR-selective agonists / antagonists. This review summarizes recent advances in the structures, biological functions, and possible clinical use of our synthetic RARs and RXRs hgands.

View full abstract

Show abstractHide abstract

In 1981, Suda and colleagues reported the differentiation-inducing activities of calcitriol. Several companies and organic chemists initiated the synthesis of vitamin D analogs with the aim to separate the calcemic actions of calcitriol from its actions on regulating the cell growth and differentiation. The group of Chugai company succeeded in marketing OCT, Oxarol, as a therapeutic agent for secondary hyperparathyroidism and psoriasis, and Leo company, MC-903, Dovonex, as a drug for psoriasis. The work on OCT and MC-903 vigorously stimulated research world-wide in the development of vitamin D analogs into pharmaceutical products without inducing hypercalcemia. New many non-calcemic vitamin D analogs are being developed. D-hormone is widely accepted as being an antiresorptive drug in bone The anabolic effects of alfacalcidol were confirmed in vitamm-D repleted rats In bone, alfacalcidol, also calcitriol, acts independently of its effects on intestinal calcium absorption and the resultant suppression of PTH. The new vitamin D analogs, ED-71 and 2-MD, which had a potent effect on bone formation, markedly increased bone mass and bone strength in OVX rats When the biological properties of ED-71 and 2-MD were compared, big differences were observed. Judging from these observations, it is impossible to explain about the mechanism of bone formation by D-hormone analogs. Recently, another unexplamable reports appeared. In spite of no binding activities of 19-nor-OCT to the vitamin D receptor (VDR), it is able to induce 25-hydroxyvitamin D 24-hydroxylase depending on VDR Non-steroidal vitamin D analogs such as CD-483 and carborane analogs showed the vitamin D like biological activities. Examining about these results in vitamin D metabolites, and we should think about the criteria of vitamin D.

View full abstract

Download PDF (815K)

To clarify the mechanism of regulation of oc-Tocopherol Transfer Protein (αTTP), various model rats were used to analyze the liver αTTP and its mRNA in this study. Developmental changes in the expression of αTTP after birth were investigated in rats. During the suckling period, the plasma α-/γ-tocopherol ratio linearly increased This increase seemed to correlate with the developmental expression of αTTP in the liver during this period. The expressions of αTTP and its mRNA were about 30 % lower in E-replete rats than in normal E rats In E-depleted rats, however, αTTPmRNA level increased to about 150 % of that in the normal E rats These findings indicate that the synthesis of αTTP can be regulated by the vitamin E nutritional status. The expression of hepatic αTTP gradually increased in Streptozotosm (STZ)-mduced diabetic rats with decreased plasma E/total lipids ratio compared with control rats. This increase suggests the adaptation against oxidative stress. Oppositely, the expression of hepatic αTTP is decreased in another oxidative stress, hyperoxia. The expression of αTTP studied in various culture cell lines, such as cervical, ovarian, gastric, and colon cancers was observed in some cases. Further studies are required for clarifying the significance of αTTP other than the antioxidant function.

View full abstract

Recent studies have suggested that vitamin K deficiency influences not only blood coagulation system but also bone metabolism. To prevent fracture, higher vitamin K intake may be required than to maintain the blood coagulation system. Currently, among vitamin K_2 homologues, MK-4 is used to treat osteoporosis in clinical practice. It has been reported that MK-4 inhibits bone resorption, and promotes bone formation in in vitro systems. In animal experiments, the results of histological evaluation also supported the above findings. Furthermore, the effects of MK-4 on bone mineral content (BMC) and bone strength were compared using several animal models. As a result, MK-4 not only improved bone strength in response to BMC, but also improved bone strength without affecting BMC in some models. In a clinical study, it has been reported that MK-4 is more effective for reducing the incidence of fracture than for improving bone mineral density These results suggest that MK-4 may improve bone quality.

View full abstract

Register with J-STAGE for free!