1,25-Dihydroxycholecalciferol hormone synthesis

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

Parathyroid hormone acts chiefly on kidney increasing renal tubular resorption and bone resorption of calcium it increases calcium absorption from the gut, indirectly, by stimulating the renal synthesis of la-25-dihydroxycholecalciferol (see Vitamin D). It increases the rate of bone remodelling (mineral and collagen) and osteocyte activity with, at high doses, an overall balance in favour of resorption (osteoclast activity) with a rise in plasma calcium con-... 

Another important hormone derived from cholesterol is vitamin D. This steroid-like hormone is involved in regulating calcium and phosphorus metabolism. The complete synthesis of vitamin D requires ultraviolet light to convert 7-dehydrocholesterol to previtamin Dj. The reaction scheme is shown in Figure 34-3. The active hormone 1,25-dihydroxycholecalciferol (calcitriol)... 

The metabolic acid-base balance affects the sensitivity of bone to parathyroid hormone (PTH) and the synthesis of 1,25-dihydroxycholecalciferol. Therefore, acknowledging this when balancing the mineral content of the diet can have an effect on the incidence of milk fever. Conditions that promote an alkalotic state (high dietary cations, Na and IC ) reduce the sensitivity of bone to PTH and can limit the release of calcium. Conversely, an acidotic state (high dietary anions, CP and S ) increases the sensitivity to PTH, increases 1,25-dihydroxycholecalciferol production and hence increases the calcium supply. Through these metabolic responses, manipulation of the acid-base balance in the diet of the pre-calving cow has been successful in reducing the incidence of milk fever. 

Dihydroxycholecalciferol is able to act on a number of tissues with columnar epithelial cells, including intestinal mucosa, kidney tubules, the shell gland of birds and probably also various types of bone cell where it may assist the synthesis of osteocalcin (page 161). Its mode of action is very similar to that of steroid hormones (Figure 30.1). In this respect its precursor, vitamin Dj, may be considered to function as a prohormone rather than a vitamin. The ability of 1,25-DHCC and other metabolites of vitamin D3 to act on bone and kidney cells, as well as those of the intestine, means that vitamin D plays a key role in calcium and phosphorus metabolism (Hgure 30.2). 

Although it is generally agreed that steroid and thyroid hormones act in the nucleus of the target cell to induce specific protein synthesis, there are data which suggest that thyroid hormone (Sterling, 1979) and 1,25-dihydroxycholecalciferol (Bikle et al., 1979) may also act via extra-nuclear mechanisms. 

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