Cholesterol steroid hormones derived from

FIGURE 21-46 Some steroid hormones derived from cholesterol. The... 

The steroid hormones, derived from cholesterol, include the adrenal cortical hormones (e.g., cortisol, aldosterone, and the adrenal sex steroids dehy-droepiandrosterone [DHEA] and androstenedione) and the gonadal hormones (e.g., the ovarian and testicular sex steroids, such as testosterone and estrogen). 

Testosterone A male sex hormone that is produced in the testes. It plays a central role in the development of secondary sex characteristics. It is a steroid hormone derived from cholesterol. 

The distribution of LDL to various tissues may depend on the rate of transcapillary transport as well as the activities of the LDL receptors on the cell surface. Adipose tissue and muscle have few LDL receptors and take up LDL only slowly, whereas adrenal gland (important in the synthesis of steroid hormones derived from cholesterol) has a highly fenestrated epithelium with abundant receptors and takes up LDL avidly. Much of our understanding of the pathway of receptor-mediated uptake of LDL has been derived by studying cultured cells, mainly fibroblasts, smooth muscle cells and macrophages. As far as is known the behaviour of the LDL receptor in vivo is generally consistent with that observed in cultured cells. 

Cholesterol is an extremely important biological molecule that modulates the fluidity of animal cell membranes and is the precursor of steroid hormones (such as progesterone, testosterone, oestradiol and cortisol) and bile acids. Cholesterol is either derived from the diet or synthesised de novo. Regardless of the source, cholesterol is transported through the circulation in lipoprotein particles, as are cholesterol esters, the cellular storage form of cholesterol. The amount of cholesterol synthesised daily in the liver of a normal person is usually double that obtained from dietary sources. Other sites of cholesterol synthesis include the intestine, and the degree of production is highly responsive to cellular levels of cholesterol. Over 1.2 g of cholesterol is lost in the faeces daily in the form of free sterol or as bile acids. 

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)... 

Steroids are a femily of lipid molecules that includes cholesterol, steroid hormones, and bile salts. These amphipathic molecules (containing both hydrophobic and hydrophilic regions) are derived from two-carbon acetyl-CoA... 

Steroids are derived from isoprene via squalene, and all share the same core stmcture it is a fused ring that is essentially planar (Fig. 3-21). Sterols are steroids that contain one or more hydroxyl groups. E.g., cholesterol is an abimdant component of cytoplasmic membranes of animal cells and is the precursor of the hormone testosterone. 

Steroids Compounds derived from cholesterol (itself also a steroid), most of which are hormones. 

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

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. 

Cholesterol is a major constituent of the cell membranes of animal cells (see p. 216). It would be possible for the body to provide its full daily cholesterol requirement (ca. 1 g) by synthesizing it itself However, with a mixed diet, only about half of the cholesterol is derived from endogenous biosynthesis, which takes place in the intestine and skin, and mainly in the liver (about 50%). The rest is taken up from food. Most of the cholesterol is incorporated into the lipid layer of plasma membranes, or converted into bile acids (see p. 314). A very small amount of cholesterol is used for biosynthesis of the steroid hormones (see p. 376). In addition, up to 1 g cholesterol per day is released into the bile and thus excreted. 

It is well known that the steroid hormones in mammals are biosynthesized from cholesterol. This compound is derived from the acetate-mevalonate pathway through the monoterpene geranyl pyrophosphate, which undergoes several enzymatic reactions to form the triterpene squalene. 

The biosynthesis of steroids is complex, as one wonld expect since all the compounds in this group must be derived from a single precnrsor (cholesterol (5.4)). The primary sonrce of all the compounds involved in steroid synthesis is acetate, in the form of acetyl-coenzyme A. Cholesterol, besides being ingested in food, is synthesized in large amounts, and an adnlt human contains about 250 g of cholesterol. In contrast, the steroid hormones are produced at the milligram level or lower. 

T FIGURE 10-19 Steroids derived from cholesterol. Testosterone, the male sex hormone, is produced in the testes. Estradiol, one of the female sex hormones, is produced in the ovaries and placenta. Cortisol and aldosterone are hormones synthesized in the cortex of the adrenal gland they regulate glucose metabolism and salt excretion, respectively. Prednisolone and prednisone are synthetic steroids used as antiinflammatory agents. 

We begin with an account of the main steps in the biosynthesis of cholesterol from acetate, then discuss the transport of cholesterol in the blood, its uptake by cells, the normal regulation of cholesterol synthesis, and its regulation in those with defects in cholesterol uptake or transport. We next consider other cellular components derived from cholesterol, such as bile acids and steroid hormones. Finally, an outline of the biosynthetic pathways to some of the many compounds derived from isoprene units, which share early steps with the pathway to cholesterol, illustrates the extraordinary versatility of isoprenoid condensations in biosynthesis. 

The steroid hormones (glucocorticoids, mineralocorticoids, and sex hormones) are produced from cholesterol by alteration of the side chain and introduction of oxygen atoms into the steroid ring system. In addition to cholesterol, a wide variety of isoprenoid compounds are derived from mevalonate through condensations of isopentenyl pyrophosphate and dimethylallyl pyrophosphate. 

Steroid Hormones Are Derived from Cholesterol The Circulating Hormone Concentration Is Regulated Hormone Action Is Mediated by Receptors... 

Most hormones fall into three classes Polypeptides, steroids, and amino acid derivatives. Polypeptide hormones are synthesized from large precursors. Steroid hormones are derivatives of cholesterol. Thyroid hormones and epinephrine are amino acid derivatives. 

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