Vitamin endocrine system

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). 

NORMAN A w (1990) The vitamin D endocrine system in bone , in Pecile, A and de Bernard, B (eds). Bone regulatory factors. New York, Plenum Press. 

Because the vitamin D-endocrine system is responsible in large part for the maintenance of extra- and intracellular calcium homeostasis, it is reasonable to conclude that the interference of lead with renal... 

Bouillon R, Okamura HO, Norman AW (1995) Structure-function relationship in the vitamin D endocrine system. Endocr Rev 16 200... 

Calcium is present in three forms e.g., as free calcium ion, bound to plasma protein albumin and in diffusable complexes. The endocrine system, through parathyroid hormone and calcitonin, helps in keeping the concentration of ionized plasma calcium in normal level. Decrease in plasma levels of ionized calcium leads to increased parathyroid hormone secretion. Parathyroid hormone tends to increase plasma calcium level by increasing bone resorption, increasing intestinal absorption and increasing reabsorption of calcium in kidney. Vitamin D acts by stimulating... 

Fig. 1. Vitamin D endocrine system. Vitamin D, obtained either through the diet or by conversion of 7-dehydrocholesterol in the skin, is sequentially hydroxylated in the liver and kidney to produce the active metabolites la,25(OH)2D, and 24R,25(OH)2D,.

In the past few years, due to a number of technological improvements, l,25(OH)2D3 receptors were able to be identified in a very wide range of tissues and cell lines, extending by far the classical limits of the vitamin D actions upon calcium metabolism (see Ref. 2, page 507). In many of these non-classical target tissues, the reason for the presence of l,25(OH)2D3 receptors is still under active research. We will describe here the possible action of l,25(OH)2D3 in some of those new target tissues in an effort to display the complexity of the vitamin D endocrine system. 

Fig. 4. Schematic representation of the vitamin D-inicro-endocrine system (stem cell differentiation) showing the localization of l,25(OH)2D3 receptors as well as cells which have been shown to synthesize l,25(OH)2D.,.

N8. Norman, A. W., Roth, J., and Orci, L., The vitamin D endocrine system steroid metabolism, hormone receptors, and biological response (calcium binding proteins). Endocr. Rev. 3, 331-366 (1982). 

A significant amount of 7-dehydrochoIesteroI is also found in the deeper dermis layer, but because most UVB photons are absorbed by the epidermis, very little production of vitamin D3 occurs in the dermal layer. There is some evidence that formation of 7-dehydrocholesterol is under the regulation of the vitamin D3 endocrine system [39] however, details of this regulation are not fully understood. 

Norman AW, Henry HL, Bishop JE, Song XD, Bula C, and Okamura WH (2001) Different shapes of the steroid hormone lalpha,25(OH)(2)-vitaminD(3) act as agonists for two different receptors in the vitamin D endocrine system to mediate genomic and rapid responses. Steroids 66,147-58. 

Norman AW, Ishizuka S, and Okamura WH (2001) Ligands for the vitamin D endocrine system different shapes function as agonists and antagonists for genomic and rapid response receptors or as a ligand for the plasma vitamin D binding protein./owma/ of Steroid Biochemistry and Molecular Biology 76, 49-59. 

Other endocrine. systems are interrelated. Both corticosteroids and thyroid hormones may increa.se the requirement for pyridoxine and affect pyridoxal S-phosphate-dependent metabolic processe.s. Moreover, there appear to be associations between vitamin B(, and anterior pituitary hormones that seem to involve the hypothalamu.s. S-hydroxytiypta-mine. and dopamine. The latter two neurotransmitters are synthc.sizcd by metabolic procetises that require pyridoxal S-phosphate. 

Reichel H, Koefiier HP, Norman AW. The role of the vitamin D endocrine system in health and disease. 

It is a well-known fact that fractional absorption of calcium in man ranges from 20 to 70% (Heaney etal. 1990). A number of studies have also shown there to be a decrease in the rate of fractional absorption of calcium with increasing age (for a review, see Armbrecht 1990). Adaptation of intestinal calcium absorption to changes in calcium intake via the vitamin D endocrine system has also been demonstrated in human subjects (Sheikh etal. 1990). A low serum Ca level stimulates the renal synthesis of 1,25(OH)2Dj (Fraser 1980), which in turn leads to increased absorption of calcium from the intestinal lumen. It is through this mechanism that the fractional absorption of calcium from the intestine... 

This report summarizes the current status of the vitamin D endocrine system, focussing on its biochemical aspects. For more detailed treatments of the subject and for discussions of the older literature and of clinical and chemical results, earlier reviews should be consulted.1... 

Pig. 5. Diagramatic repiesentation of calcium homeostatic mechanisms involving the vitamin D endocrine system located in the kidney. Note that the calcium sensing organs are the para-thryoid glands (hypocalcemia) and the C-cells of the thyroid (hypercalcemia). Note that the vitamin D hormone acts by itself on the intestine and together with parathyroid hormone in bone and kidney... 

It is now clear that the vitamin D endocrine system is a major factor in the control of plasma calcium and the overall calcium economy of terrestial vertebrates The parathyroid glands monitor calcium concentration of the plasma (Fig. 5) and in response to low blood calcium secrete the parathyroid hormone Parathyroid hormone is taken up by the kidney and bone In the kidney, parathyroid hormone stimulates production of 1,25-(OH)2D3 The 1,25 (OH)2D3 then... 

It is obvious that a variety of disorders would result from a disturbance of the vitamin D endocrine system. Fat malabsorption would result in a deficiency of vitamin D giving rise ultimately to osteomalacia or rickets or secondary hyperparathyroidism. A hepatic disorder such as severe cirrhosis, or biliary atresia, may result in malabsorption of vitamin D and defective vitamin D-25-hydroxylation. Dilantin and phenobarbital cause low plasma 25-OH-D levels resulting in rickets and osteomala-cia246) Qf parathyroid glands would cause a severe hypocalcemia and tetany. 

The elucidation of the biochemistry of the vitamin D endocrine system has led to a renewed interest in the synthetic aspects of the field. Because of the limited availability of vitamin D metabolites from natural sources, the production of large quantities of metabolites and analogs is essential for detailed biomedical experimentation. Vitamin D analog synthesis has not only aided in determining the structural and stereochemical parameters of the natural metabolites, but has also helped to establish a foundation for structure-activity theories. 

---