Steroid hormones and vitamin

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

The most frequent protein in the plasma, at around 45 g is albumin. Due to its high concentration, it plays a crucial role in maintaining the blood s colloid osmotic pressure and represents an important amino acid reserve for the body. Albumin has binding sites for apolar substances and therefore functions as a transport protein for long-chain fatty acids, bilirubin, drugs, and some steroid hormones and vitamins. In addition, serum albumin binds Ca "" and Mg "" ions. It is the only important plasma protein that is not glycosylated. 

Albumin is the main plasma protein, with a molecular weight of about 69 kDa, and is important for normal plasma oncotic pressure and the transport of many biologically active substances, including free fatty acids, phospholipids (e.g., lysophosphatidic acid), prostanoids, heavy metals, steroid hormones, and vitamins. Albumin-bound lysophosphatidic acid serves as a survival factor for cultured mouse proximal tubular cells (L4). Lysophosphatidic acid is an exquisitely potent inhibitor of apoptosis, comparable with growth factors, for example, EGF. The influence of lysophosphatidic acid on the survival of tubular cells depends on the activation of phophatidylinositol 3-kinase (PI3K) with subsequent activation of Akt and pp70s6k. pp70s6k is a rapamycin-inhibited kinase, which plays an important role in the cellular proliferation. Lysophosphatidic acid also serves as a proliferation factor of mouse proximal tubular cells. Further albumin-bound factors important for the survival of the proximal tubular cells are phosphatidic acid... 

Cholesterol (Figure 6.12) is a very common starting point for making many interesting compounds essential to our bodies.3 These include bile acids (which help dissolve cholesterol in ingested food), steroid hormones and vitamin D (note some... 

Mammalian nuclear receptors for steroid hormones (SHRs) are of great importance in physiology and medicine, because they control not only developmental pathways but also regulate central physiological and metabolic functions in the adult organism. Steroid hormones and vitamin D are derivatives of cholesterol. Structures of vitamin D3 and of... 

Cholesterol is a precursor for other important steroid molecules the bile salts, steroid hormones, and vitamin D. 

Cholesterol (3-hydroxy-5,6-cholestene) belongs to a family of compounds derived from a fused, reduced, nonlinear four-ring system of cyclopenta(a -phenanthrene. Bile adds, steroid hormones, and vitamin D metabolites are derivisd from diolesterol. 

The answer is b. (Murray, pp 505-626. Scrivei, pp 5029-5250. Sack, pp 121-138. Wilson, pp 287-320.) Steroid hormones such as aldosterone are ultimate derivatives of cholesterol. The compound illustrated in the question is cholesterol, one of a large group of steroids. Cholesterol, which can be derived from the diet as well as synthesized de novo, is the precursor of all steroids involved in mammalian metabolism. These include the bile acids, the steroid hormones, and vitamin D. Cholesterol cannot be metabolized to carbon dioxide, and water in humans. It must be excreted as a component of bile. Adrenocorticotropin (ACTH) is a peptide hormone of the adenohypophysis that influences the secretion of corticosteroid hormones. Prostaglandins are eicosanoid derivatives that are also made up of... 

Cholesterol serves as the biosynthetic precursor for several vital compounds, including a variety of steroid hormones and bile acids. Many of these compounds, and many other polyisoprenoid compounds biosynthetically related to cholesterol, act biologically as important regulatory compounds [105]. In mammals such regulatory compounds include steroid hormones and vitamins A and D. Steroids and other isoprene derivatives also play important regulatory roles in other phyla. Several insect hormones, for example, are isoprenoid derivatives [106] (cf. Chapter 8). Memy of the floral scents of plants are isoprene derivatives. 

An important raw material for the partial synthesis of steroid hormones (and Vitamin D) is cholesterol, which (prior to the BSE crisis) was isolated from the spinal cord of cattle. Another important source is the fat in sheep s wool (lanolin), which contains around 15 % of cholesterol. Among the plant sterols, stigmasterol is of great economic significance as the starting material for the partial synthesis of steroids. It is contained from 12 to 25 % in the non-hydrolysable... 

Summary term for a number of steroid hormones and their precursors with differentiation-inducing activity in many tissues. As regards bone, three components are relevant cholecalciferol ( vitamin D ) 25-hydroxyvi-taminD3 (calcidiol) and 1,25-dihydroxy vitamin D3 (calcitriol). The latter is the biologically active form and increases both intestinal calcium absoiption and bone resorption. Vitamin D preparations are widely used for the treatment of osteoporosis. Daily supplementation with vitamin D reduces bone loss in postmenopausal women and hip fractures in elderly subjects. 

The signal crosses the membrane and activates gene transcription. Signals for soluble receptors include steroid hormones, retinoic acid, thyroid hormone, and vitamin D. 

Retinoids are a family of naturally occurring and synthetic analogues of vitamin A. The skin of subjects deficient in vitamin A becomes hyperplastic and keratotic (phrynoderma, or toad skin). While natural vitamin A is occasionally employed therapeutically, synthetic retinoids are more effective and represent a major advance in dermatological pharmacotherapy. Retinoids have myriad effects on cellular differentiation and proliferation it is likely that nuclear retinoic acid receptors mediate these effects by activating gene expression in a manner analogous to receptors for steroid hormones and thyroid hormones. Despite a common mechanism of action, however, retinoids vary widely in their physiological effects. 

Ligands of the RXR-heterodimer group and the orphan receptors are chemically more diverse than the ligands of the steroid family. Representative hgands of this group are the retinoids all-trans retinoic acid, 9-cis retinoic acid, the T3 hormone and vitamin D3 (fig. 4.1). 

Many steroids have an alcoholic hydroxyl attached to the ring system, and are known as sterols. The most common sterol is cholesterol, which occurs in most animal tissues. There are many different steroid hormones, and cholesterol is the precursor for all of them. Cholesterol is also the precursor of vitamin D. 

The ABC1 protein is a member of a large family of multidrug transporters, sometimes called ABC transporters because they all have ATP-binding cassettes they also have two transmembrane domains with six transmembrane helices (Chapter 11). These proteins actively transport a variety of ions, amino acids, vitamins, steroid hormones, and bile salts across plasma membranes. The CFTR protein that is defective in cystic fibrosis (see Box 11-3) is another member of this ABC family of multidrug transporters. 

The fundamental role of ascorbic acid in metabolic processes is not well understood. There is some evidence that it may be involved in metabolic hydroxylation reactions of tyrosine, proline, and some steroid hormones, and in the cleavage-oxidation of homogentisic acid. Its function in these metabolic processes appears to be related to the ability of vitamin C to act as a reducing agent. 

Niacin and pantothenic acid synergistic wilh ACTH in steroid hormone synthesis Vitamin D antagonized directly by AC-TH via cortisol action... 

Dietary vitamin A is stored in the liver and secreted into the bloodstream when needed. The circulating retinol is taken up by target cells and oxidized in part to retinoic acid, which induces the synthesis of proteins through the direct control of gene expression. This type of action—gene activation—establishes vitamin A (in the form of its metabolite, retinoic acid) as a hormone, similar to the steroid hormones and the thyroid hormone. 

Vitamin D can be considered both a hormone and a vitamin. Its mode of action is like that of other steroid hormones, and it is synthesized in the body. It can be given in the diet (e.g., in supplemented milk) and would then be called a vitamin. 

Lipid-soluble hormones act usually by gene activation/deactivation. Examples of these hormones include steroids, thyroid hormone, and vitamin A (retinoic acid). The hormones are transported through the circulation in association with a hormone-binding protein and are soluble in the plasma membrane of the cell. Their receptors are intracellular, and they act on gene transcription (the synthesis of messenger RNA) rather than at the protein level. Thus, they act more slowly than do the soluble hormones, on the scale of days rather than minutes. 

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