[Vitamin D3--a prodrug of different D3-hormones]

Vitamin D (colecalciferol) is critically important for the development, growth, and maintenance of a healthy skeleton from birth until death. Vitamin D is metabolized in the liver to 25-hydroxy-colecalciferol and then in the kidney to 1 alpha,25-dihydroxy-colecalciferol (calcitriol). Calcitriol is the dominant D(3)-hormone and produces a wide array of bio-logical responses via interacting both with the classical vitamin D nuclear receptor (VDR(nuc)) that regulates gene transcription in over 30 target organs and with a putative cell membrane receptor (VDR(mem1,25)) that mediates rapid biological responses. 24R,25-Dihydroxy-colecalciferol has been shown to be an essential D(3)-hormone for the process of bone fracture healing. It initiates its biological responses via stereospecific binding to a second cell membrane receptor, the VDR(mem24,25). The key D(3)-hormone involved in the regulation of cell proliferation in the prostate is 25-hydroxy-colecalciferol. It is mainly acting directly through the nuclear vitamin D receptor but partially also through its 1 alpha-hydroxylation in the prostate. Elderly subjects often have mean 25-hydroxy-colecalciferol levels in the insufficiency range throughout the year. The oral dose necessary to achieve adequate serum 25-hydroxy-colecalciferol levels is a daily dose of 400 IU.