Steroid hormones precursors

The following acid-catalyzed cyclizations leading to steroid hormone precursors exemplify some important facts an acetylenic bond is less nucleophilic than an olelinic bond acetylenic bonds tend to form cyclopentane rather than cyclohexane derivatives, if there is a choice in proton-catalyzed olefin cyclizations the thermodynamically most stable Irons connection of cyclohexane rings is obtained selectively electroneutral nucleophilic agents such as ethylene carbonate can be used to terminate the cationic cyclization process forming stable enol derivatives which can be hydrolyzed to carbonyl compounds without this nucleophile and with trifluoroacetic acid the corresponding enol ester may be obtained (M.B. Gravestock, 1978, A,B P.E. Peterson, 1969). 

Androstenedione Steroid Hormone precursor Converted to estrogens and testosterone... 

Dehydroepiandrosterone Steroids Hormone precursors Converted to estrogens and... 

Cholesterol is one of the most highly recognized molecules in human biology, in part because of a direct relationship between its concentrations in blood and tissues and the development of atherosclerotic vascular disease Cholesterol, which is transported in the blood in Upoproteins because of its absolute insolubility in water, serves as a stabilizing component of cell membranes and as a precursor of the bile salts and steroid hormones. Precursors of cholesterol are converted to ubiquinone, dolichol, and, in the skin, to cholecalciferol, the active form of vitamin D. As a major component of blood lipoproteins, cholesterol can appear in its free, unesterifiedform in the outer shell of these macromolecules and as cholesterol esters in the lipoprotein core. 

A number of oxysterols, which suppress HMGR when added to cell cultures, are natural precursors of cholesterol or products of its metabolism to bile acids or steroid hormones [18]. These sterols include the bile acid intermediates 7a- and 26-hydroxycholesterol, the steroid hormone precursors 20a- and 22R-hydroxycholesterol. 24(s)-hydroxycholesterol (cerebrosterol) was foimd by Kandutch et al [18] that other oxysterol metabolites capable of repressing the reductase may also be produced. Kandutch et al [18] foimd several unidentified oxysterols capable of suppressing activity in extracts of cultured cells. Inhibitory oxysterols are, therefore, produced in all cells that synthesize cholesterol as an end product, as well as in cells that synthesize cholesterol and metabolize it to other steroid products. 

Adrenocortical Tumors. Virilization, hypercortisolism, feminization, abdominal pain, palpable abdominal tumor, or combinations of these features are clinical symptoms of adrenocortical tumors. Both types of adrenocortical tumors (carcinoma and adenoma) can produce a wide variety of steroid hormones. This is a consequence of multiple enzyme deficiencies in tumor tissues. The tumor cells are capable of synthesizing large amounts of steroid hormone precursors independent of ACTFI stimulation. Excessively high amounts of DHEA and other 3p hydroxy-5-ene steroids characterize the urinary steroid profile in children with adrenocortical carcinoma, but similar profiles can also be produced by adrenal adenomas. Elevated lip hydroxy-androsterone excretion alone or combined with high excretion of cortisol metabolites or 3p hydroxy-5-ene steroids are characteristic of the urinary steroid profile for adrenocortical adenomas [36,37]. 

FIGURE 25.43 The steroid hormones are synthesized from cholesterol, with intermediate formation of pregnenolone and progesterone. Testosterone, the principal male sex hormone steroid, is a precursor to /3-estradiol. Cortisol, a glucocorticoid, and aldosterone, a mineralocorticoid, are also derived from progesterone. 

Pregnenolone and Progesterone Are the Precursors of All Other Steroid Hormones... 

Terpenes (and terpenoids) are further classified according to the number of 5-carbon units they contain. Thus, monoterpenes are 10-carbon substances biosynthesized from two isoprene units, sesquiterpenes are 15-carbon molecules from three isoprene units, diterpenes are 20-carbon substances from four isoprene units, and so on. Monoterpenes and sesquiterpenes are found primarily in plants, but the higher terpenoids occur in both plants and animals, and many have important biological roles. The triterpenoid lanosterol, for example, is the precursor from which all steroid hormones are made. 

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 ceUular source of the various ovarian steroids has been difficult to unravel, but a transfer of substrates between two cell types is involved. Theca cells are the source of androstenedione and testosterone. These are converted by the aromatase enzyme in granulosa cells to estrone and estradiol, respectively. Progesterone, a precursor for all steroid hormones, is produced and secreted by the corpus luteum as an end-product hormone because these cells do not contain the enzymes necessary to convert progesterone ro other steroid hormones (Figure 42-8). 

H)2-D3 is produced by a complex series of enzymatic reactions that involve the plasma transport of precursor molecules to a number of different tissues (Figure 42-9). One of these precursors is vitamin D—really not a vitamin, but this common name persists. The active molecule, l,25(OH)2-D3, is transported to other organs where it activates biologic processes in a manner similar to that employed by the steroid hormones. 

Cholesterol, mostly esterified, is utilized in the buildup of cell biomembranes. Besides, cholesterol is a precursor to biologically important steroid compounds bile acids (in liver), steroid hormones (in adrenal cortex, male and female sexual glands, and placenta), and vitamin D3, or cholecalciferol (in skin). 

Cholesterol the steroid precursor of all steroid hormones in humans and a critical component of biological membranes. 

Figure 12.1 Location in the body of some glands. The pineal secretes melatonin, which is discussed in Chapter 14. Skin should be included since it secretes a precursor of vitamin D, now considered to be a steroid hormone.

Ultraviolet light causes a chemical change in dihydrocholesterol to produce cholecalciferol, a precursor of vitamin D. The latter conforms better to the definition of a steroid hormone than a vitamin. Indeed, the classification of vitamin D as a vitamin is an historical accident. The precursor is released from the skin and is further modified in the liver and kidney to form dihydroxycholecalciferol, which is the active form of the hormone (see Chapter 15 for the reactions). It increases calcium absorption from the... 

The follicular phase covers the development of the follicle, which involves an increase in its size due to an increase in follicular fluid, growth of the ovum (i.e. an increase in the contents of RNA and protein) and an increase in the number of cells that surround the ovum. These cells are of two types, the granulosa and the thecal cells. The role of these cells is to synthesise and secrete the steroid hormones oestrogens (mainly oestradiol). The precursor molecule for their synthesis is cholesterol. There is a division of labour between these cells the thecal cells convert cholesterol into the male sex hormones androstenedione and testosterone, which are released into the blood to be taken up by the granulosa cells where they are converted to the oestrogens (Figure 19.8). For details of pathways, see Appendix 19.1. 

The effects of the steroid hormone calcitriol (see p. 330) in bone are complex. On the one hand, it promotes bone formation by stimulating osteoblast differentiation (top). This is particularly important in small children, in whom calcitriol deficiency can lead to mineralization disturbances (rickets see p.364). On the other hand, calcitriol increases blood Ca "" levels through increased Ca "" mobilization from bone. An overdose of vitamin D (chole-calciferol), the precursor of calcitriol, can therefore have unfavorable effects on the skeleton similar to those of vitamin deficiency (hypervitaminosis see p.364). 

Lipids are important components of the diet fatty acids are the higher energetic source as they ensure 9kcal/g. Furthermore, some peculiar fatty acids themselves and several components of the unsaponifiable fraction are biologically active molecules, as they can act as vitamins (tocopherols— vitamin E), provitamins (carotenes—vitamin A, cholecalcipherol—vitamin D), vitamin-like (essential fatty acids), and hormones or hormone precursors (sterols—steroidal hormones). 

D. Cholesterol is not only an important contributor to the structural properties of cell membranes, but it is also the precursor for steroid hormone synthesis and a major component of the lipoproteins. 

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