Vitamin D: The secosteroid hormone and (PDF Download Available)
Rosen 1 , in Vitamin D Third Edition , This multifunctional molecule directly and indirectly regulates calcium metabolism but also has been found to be important in energy balance. Chronic diseases such as obesity, diabetes mellitus, and atherosclerosis have been linked to changes in circulating levels of the vitamin D metabolite 25 OH D. This chapter focuses on the relationship of vitamin D and its receptor to global energy expenditure and body composition.
Several mechanisms are examined relative to the effects of vitamin D storage on adipose tissue and its role in regulating fatty acid and glucose metabolism.
Ryoko Okamoto 1 , H. The secosteroid hormone 1,25 OH 2 D 3 has a role in normal hematopoiesis, enhancing the activity of monocyte—macrophage differentiation. It also has anti-proliferative and pro-differentiation effects against various myeloid leukemia cell lines by both genomic and non-genomic pathways. Nevertheless, hematopoiesis in vitamin D 3 receptor deletional mice is fairly normal, suggesting the vitamin D 3 pathway has an adjunctive role in blood formation in mammals.
The anti-proliferative activities of 1,25 OH 2 D 3 in vivo require supraphysiological levels of the secosteroid. Since the mids, many vitamin D analogs have been synthesized that possess reduced hypercalcemic activity and increased ability to induce cell differentiation and to inhibit proliferation of leukemic cells.
Proof of principle that 1,25 OH 2 D 3 and its analogs are beneficial in leukemia has been shown in experiments conducted in vitro and in laboratory animals, but to date their therapeutic value in patients is unproven. Uitterlinden, in Vitamin D Third Edition , The secosteroid hormone vitamin D, vitamin D receptor VDR , and the metabolizing enzymes involved in the formation of the biologically active form of the hormone, acting together, are major players in the vitamin D endocrine system.
This system plays an important role in skeletal metabolism, including intestinal calcium absorption, but has also been shown to play an important role in other metabolic pathways, such as those involved in the immune response and cancer. The interpretation of polymorphic variations in candidate genes of the vitamin D endocrine system such as the VDR gene or the DBP gene is severely hindered by the fact that, until recently, only few polymorphisms in these genes were studied.
To understand the mechanisms underlying the associations, one has to analyze the genomic organization of the loci, to identify which genes are present in the chromosomal area, to categorize all relevant polymorphisms, to determine the linked alleles or haplotypes across the gene, to determine their relationship with the markers used so far, and, finally, to perform association analyses with relevant phenotypic endpoints such as disease.
The secosteroid hormone 1,dihydroxyvitamin D 3 1,25 OH 2 D 3 is the most potent metabolite of vitamin D 3 and is an important regulator of calcium homeostasis and bone metabolism via actions in intestine, bone, kidney, and parathyroid glands.
Throughout the last few decades it has become evident that the vitamin D receptor VDR is not limited to cells and tissues involved in regulation of calcium and bone metabolism but is also present in a wide variety of other cells and tissues including cancer cells of various origins.
This has led to a vast series of studies on the role of vitamin D in tumor cell growth regulation, treatment of cancer and development of potent synthetic vitamin D analogs. Various specialized chapters will discuss in detail the effect of vitamin D on specific cancers see chapters in Section X and the development of analogs see chapters in Section IX. In this chapter our goal is to set the stage by providing an overview of the history and current state of knowledge of the field.
We will address several areas: Vitamin D has a secosteroid structure in which a bond C9—C10 in ring B of the steroid structure is broken. Vitamin D 3 and vitamin D 2 are produced by the photochemical reaction of 7-dehydrocholestrol and ergosterol with ultraviolet light B naturally with sunlight , and subsequent heat isomerization, respectively. These two chemical reactions not enzymatic reactions are essential for vitamin D synthesis. In human, these reactions of 7-dehydrocholestrol occur in the skin.
The structural difference between vitamin D 3 and vitamin D 2 is in their side chains Figure Steroid hormones and the secosteroid, vitamin D, belong to an ancient family of signaling molecules with diverse functions, including central roles in the regulation of female and male reproductive processes. The human steroid hormones are derived from cholesterol, an abundant plasma lipid and a structural component of plasma membranes and other organelles.
Seemingly subtle modifications of the four fused rings of the sterol skeleton and side chain result in molecules with different and diverse activities. This chapter reviews the general features of the synthesis and metabolism of steroid hormones, the ways in which these processes are controlled physiologically, the ways in which these processes can be modified by pharmacological intervention, and some genetic disorders that interfere with normal steroid synthesis and metabolism.
Vitamin D is a secosteroid whose actions are dependent on specific metabolic steps catalyzed by cytochrome P enzymes CYPs. The first of these steps occurs in the liver and involves the enzyme vitamin D 3 hydroxylase CYP2R1 , which catalyzes synthesis of hydroxyvitamin D 3 25 OH D 3 , the main circulating form of vitamin D. Vitamin D is a secosteroid hormone that regulates many biological functions in addition to its classical role in maintaining calcium homeostasis and bone metabolism.
Vitamin D deficiency appears to predispose individuals to increased risk of developing a number of cancers. Compelling epidemiological and experimental evidence supports a role for vitamin D in cancer prevention and treatment in many types of cancers. Preclinical studies show that 1,25D 3 , the active metabolite of vitamin D, and its analogs have antitumor effects in vitro and in vivo through multiple mechanisms including the induction of cell cycle arrest, apoptosis, differentiation and the suppression of inflammation, angiogenesis, invasion, and metastasis.
In this review, the antitumor effects of 1,25D 3 and the potential underlying mechanisms will be discussed. The current findings support the application of 1,25D 3 in cancer prevention and treatment.
Vitamin D is a secosteroid prohormone generated in the skin through photolysis of 7-dehydrocholesterol by UV light or ingested with food. The biologically active form is achieved through a two-step hydroxylation. The first reaction occurs largely in the liver to produce hydroxy vitamin D calcidiol.
This molecule circulates bound to a specific transport protein and is indicative of vitamin D status. Vitamin D receptors VDRs have been found in many tissues and organs. With regard to the skeletal muscle, the activation of nuclear VDR initiates a genomic pathway that modulates the transcription of genes involved in calcium uptake, phosphate transport, phospholipid metabolism, and satellite cell proliferation and terminal differentiation . Binding of vitamin D to cell surface VDR triggers a nongenomic pathway involved in calcium transport and protein synthesis .
Low serum levels of vitamin D are commonly observed in advanced age. Vitamin D deficiency has been associated with a multitude of negative health outcomes, including osteoporosis, diabetes mellitus, cancer, cardiovascular disease, cognitive decline, multiple sclerosis, and greater susceptibility to infections .
In addition, studies have shown that older adults with vitamin D deficiency are at higher risk of postural instability, falls, and sarcopenia [39,40].
On the other hand, supplementation with vitamin D, either alone or combined with physical exercise, improves muscle mass and function [41,42] and decreases the risk of falls . Vitamin D, a secosteroid prohormone and fat-soluble vitamin, is initially produced in the skin after ultraviolet light exposure. Many tissues in the body, including the eyes, heart, stomach, pancreas, brain, skin, gonads, and activated lymphocytes, have nuclear receptors for 1,25 OH 2 D 3.
When converting the units from nanomoles per liter to nanograms per milliliter, one should divide the concentration by 2. A summary of the most recent intake recommendations from the Institute of Medicine and The Endocrine Society are listed in Table The focus of this chapter is on the relationship between vitamin D and diabetic retinopathy. Cookies are used by this site. For more information, visit the cookies page. Volume I Francisco J. Phillip Koeffler 1 2 , in Vitamin D Third Edition , Conclusions The secosteroid hormone 1,25 OH 2 D 3 has a role in normal hematopoiesis, enhancing the activity of monocyte—macrophage differentiation.
Uitterlinden, in Vitamin D Third Edition , Publisher Summary The secosteroid hormone vitamin D, vitamin D receptor VDR , and the metabolizing enzymes involved in the formation of the biologically active form of the hormone, acting together, are major players in the vitamin D endocrine system.
Volume II Johannes P. Francesco Landi, in Molecular Basis of Nutrition and Aging , Vitamin D Vitamin D is a secosteroid prohormone generated in the skin through photolysis of 7-dehydrocholesterol by UV light or ingested with food.
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