Vitamin hormonal effects

Mechanism of Action An antibiotic that forms complexes with DNA, inhibiting DNA-directed RNA synthesis. May inhibit parathyroid hormone effect on osteoclasts and inhibit bone resorption. TherapeuticEffect Lowers serum calcium and phosphate levels. Blocks hypercalcemic action of vitamin Dand action of parathyroid hormone. Decreases serum calcium. 

Bones are constantly dissolved by osteoclasts and remineralized by osteoblasts in response to mechanical forces. Osteoclasts possess an acidic compartment and pass demineralized bone products to the periosteum (Sect. 1). They develop in stress-induced bony microcracks and are activated by differentiation factors secreted by osteoblasts, especially after menopause. Menopausal osteoporosis is controlled by drugs that are a stable form of pyrophosphate (bisphosphonate) or cathepsin K inhibitors (Sect. 2). The calcium ion concentration of blood is raised by parathyroid hormone and a vitamin D derivative called calcitriol. Parathyroid hormone causes kidneys to excrete phosphate, retain calcium, and activate calcitriol production (Sect. 3). Calcitriol induces calcium transporter proteins in osteoclasts and intestinal epithelium, where they move calcium from bone or diet into blood (Sect. 4). The chapter concludes with a discussion of calcitonin which lowers blood calcium concentrations by reversing parathyroid hormone effects on the kidney and inhibiting osteoclast activity (Sect. 5). 

The effect of vitamin D deficiency upon plasma calcium is not primarily due to malabsorption of calcium from the gastrointestinal tract. In addition to its well-known effect on calcium absorption, vitamin D contributes directly to the maintenance of plasma calcium by the skeleton by a direct action on bone similar to that of parathyroid hormone (C2, C16). The vitamin D effect may be mediated by an action on the Krebs glycolytic cycle, resulting in inhibition of citrate oxidation (S6). 

Some vitamins (A, D, E, and K) have very nonpolar molecular structures and therefore dissolve only in nonpolar solvents. In the body, the nonpolar solvents are the lipids we have classified as fats, so these vitamins are called fat-soluble. The fat-soluble vitamins have diverse functions in the body, and they act somewhat like hormones (Table 12.3). Care must be taken to avoid overdoses of the fat-soluble vitamins. Toxic effects are known to occur, especially with vitamin A, when excess amounts of these vitanfins accumulate in body tissue. Excesses of water-soluble vitamins are excreted readily through the kidneys and are not normally a problem. 

Bioassay A bioassay is a procedure for determining the concentration, purity, and/or biological activity of a substance (e.g., vitamin, hormone, plant growth factor, antibiotic, enzyme) by measuring its effect on an organism, tissue, cell, enzyme, or receptor preparation compared to a standard preparation. 

General metabolic significance. Vitamin D stimulates intestinal absorption of calcium and phosphate, renal reabsorption of these ions, deposition and mobilization of minerals in the hard tissue, controlling normal calcium and phosphate blood level by means of these processes. Molecular mechanism of the vitamin D effects most frequently conform to the effect of steroid hormones (induction of protein biosynthesis). 

Bioassay methods Bioassays are procedures that can determine the concentration of purity or biological activity of a substance such as vitamin, hormone, and plant growth factor [19]. They measure the enzyme under the influence of a vitamin and the phenotypic effects of their deficiency [18]. Bioassay methods are rarely used clinically for vitamin analysis they are most commonly used for the analysis of vitamins B12 and D [20]. There are two types of bioassays ... 

These effects of excess vitamin A are opposite from those observed in vitamin deficiency, and the changes induced in vitro by the addition of the vitamin mimic hypervitaminosis in vivo. On the basis of these observations made in cultures, it seems safe to conclude that the effects of vitamin A on the metabolism of chondroitin sulfate and on the formation of mucus are direct and do not result from the stimulation of hormonal secretion by the vitamin. The effects of vitamin A on bone and epithelium suggest that the vitamin in some way affects the biosynthesis of mucopolysaccharides, yet the effect on the bone is opposite to that on the epithelium whereas excess vitamin A accelerates the dissolution of chondroitin sulfate, it enhances mucus synthesis. 

Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. 

A standard unit of potency of a biologic agent (e.g., a vitamin, hormone, antibiotic, antitoxin) as defined by the International Conference for Unification of Formulae. Potency is based on bioassay that produces a particular effect agreed on internationally. Also called a USP unit. 

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

Interaction of vitamin D and its metaboUtes with sex hormones has been demonstrated, particularly ia birds ia which the egg-laying functions combine calcium needs and reproductive activity. The metaboUtes of vitamin D behave as hormones. As such, they play an active role ia the endocrine system, along with other hormones, to maintain the various body functions. Several biological influences of metaboUtes of vitamin D have been studied, including effects related to cancer (193—197), skin diseases (198—201), immunomodulatory effects (202,203), and Alzheimer s disease (204—206) (Fig. 9). 

Effects on Vitamin D Metabolism. Lead interferes with the conversion of vitamin D to its hormonal form, 1,25-dihydroxyvitamin D. This conversion takes place via hydroxylation to 25-hydroxyvitamin D in the liver followed by 1-hydroxylation in the mitochondria of the renal tubule by a complex cytochrome P-450 system (Mahaffey et al. 1982 Rosen and Chesney 1983). Evidence for this effect comes primarily from studies of children with high lead exposure. 

The possible mechanism kidney-induced hypertension is discussed in Section 2.4.2, Mechanisms of Toxicity. Lead appears to affect vitamin D metabolism in renal tubule cells, such that circulating levels of the vitamin D hormone, 1,25-dihydroxyvitamin D, are reduced. This effect is discussed later in this section under Other Systemic Effects. 

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