Steroid Hormones Are Derived from Cholesterol

Thyroid cells actively transport iodine (I-), which is incorporated into a few tyrosine residues of thyroglobulin by the enzyme iodoperoxidase. After condensation of iodinated tyrosine residues, the thyroglobulin is proteolytically degraded liberating thyroxine and triiodothyronine. 

Pathway of epinephrine synthesis. Epinephrine and its precursor, norepinephrine, are synthesized from tyrosine. The synthesis occurs in the chromaffin cells of the adrenal medulla and in neurons of the central and peripheral nervous system. The first step, which is catalyzed by tyrosine hydroxylase, is the rate-limiting step in the pathway. 

The step-by-step synthesis of the steroid hormones pregnenolone and progesterone from cholesterol (C27) was presented in chapter 20 (see fig 20.22). Note that pregneno-lone (C2i) and progesterone (table 20.4) (C2 ) are intermediates in the biosynthesis of all of the major adrenal steroids, including cortisol (C2i), corticosterone (C21), and aldosterone (C21). The same two compounds are intermediates in the synthesis of the gonadal steroid hormones, testosterone (C,9) and 17/3-estradiol (CI8). Because the synthesis of all these hormones follows a common pathway, a defect in the activity or amount of an enzyme along that pathway can lead to both a deficiency in the hormones beyond the affected step and an excess of the hormones, or metabolites, prior to that step. 

Deficiencies in each of the six enzymes involved in the conversion of cholesterol to aldosterone have been ob- 

Conversion of testosterone to 5ar-dihydrotestosterone (5a-DHT). Receptor-binding studies indicate that 5a-DHT has a higher affinity for the androgen receptor than testosterone does. 

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

In addition to bile salts, which facilitate the digestion of lipids, five major classes of steroid hormones are derived from cholesterol progestagens, glucocorticoids, mineralocorticoids, androgens, and estrogens. Hydroxylations by P450 monooxygenases that use NADPH and O2 play an important role in the synthesis of steroid hormones and bile salts from... 

Bile salts and steroid hormones are derived from cholesterol (see Figure 6-18). 

Steroid hormones perform many functions in cells, one of which is to activate gene expression by binding to steroid receptors, proteins in the cytoplasm that, when activated, act as factors that initiate transcription. All steroid hormones are derived from cholesterol and, as a result, have similar chemical structures. Steroid hormones differ one from another primarily in hydrox-ylation of particular carbon atoms and by aromatiza-tion of the steroid A ring of the molecule. Once a steroid hormone binds to a steroid receptor protein, the complex undergoes a series of structural changes that result in the complex binding to DNA at a particular sequence called a steroid response element (SRE)... 

The five major classes of steroid hormones are derived from cholesterol by the pathway illustrated in Figure 34-2. Hydroxylation is important in these conversions. The hydroxylation reactions require NADPH and and are carried out by the cytochrome P450 enzyme system. The enzyme 21-hydroxylase is required for the synthesis of mineralocorticoids and glucocorticoids. 

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. 

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. 

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. 

The class of lipids includes cholesterol, the bile salts and steroid hormones (which are derived from cholesterol), the fat-soluble vitamins, and compounds such as the prostaglandins. 

Steroid hormones are hormones that are derived from cholesterol. They are unusual in that they are not stored for release after synthesis. Therefore, the level of a circulating steroid hormones is controlled primarily by its rate of synthesis, which is often controlled ultimately by signals from the brain. These signals usually act through intermediary hormones. 

Bile acids are derived from cholesterol and have detergent properties which aid in fat digestion and absorption (Figure 18.4). Bile acid synthesis is the major metabolic end product of cholesterol, accounting for about half of the 800 mg/day that is made in the body. By contrast, synthesis of steroid hormones from cholesterol requires only about 50 mg/day of cholesterol. Although the body synthesizes about 400 mg of bile acids per day, closer to 20-30g of bile acids per day are secreted into the upper small intestine. To meet this need, the body recycles bile acids from the lower small intestine to the liver via enterohepatic circulation. 

Among the diverse reactions carried out by mammalian CYPs are iV-dealkylation, O-deaUcylation, aromatic hydroxylation, A-oxidation, -oxidation, deamination, and dehalogenation (Table 3-2). CYPs are involved in the metabolism of dietary and xenobiotic agents, as well as the synthesis of endogenous compounds that are derived from cholesterol e.g., steroid hormones and bile adds). 

F. 5.23. Cholesterol and its derivatives. The steroid nucleus is shown in blue. The bile salt, cholic acid, and the steroid hormone 17p-estradiol are derived from cholesterol and contain the steroid ring structure. 

Endocrine hormones are defined as compounds, secreted from specific endocrine cells in endocrine glands, that reach their target cells by transport through the blood. Insulin, for example, is an endocrine hormone secreted from the p cells of the pancreas. Classic hormones are generally divided into the structural categories of polypeptide hormones (e.g., insulin -see Chapter 6, Fig. 6.15 for the structnre of insnlin ), catecholamines such as epinephrine (which is also a nen-rotransmitter), steroid hormones (which are derived from cholesterol), and thyroid hormone (which is derived from tyrosine). Many of these endocrine hormones also exert paracrine or autocrine actions. The hormones that regnlate metabolism are discussed throughout this chapter and in snbseqnent chapters of this text. 

The naturally occurring steroids include the bile salts and various hormones. Steroids are also present as membrane constituents. They are derived from cholesterol, which is present in appreciable amounts in normal diets. 

Testosterone is a steroid. It is found in all mammals and is secreted by the testes in the male and the ovaries in the female. Estrogens function as the primary female sex hormones, although they are also present in males in lower levels. They both are derived from cholesterol through various intermediates (Figure 4.16). 

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. 

Small lipophilic (lipid-soluble) hormones diffuse across the plasma membrane and then interact with intracellular receptors in the cytosol or nucleus. The resulting hormone-receptor complex often binds to regions of the DNA and affects the transcription of certain genes (see Topic G7). Small lipophilic hormones with intracellular receptors include the steroid hormones which are synthesized from cholesterol (see Topic K5) (e.g. the female sex hormones estrogen and progesterone), thyroxine which is produced by thyroid cells and is the principal iodinated compound in animals, retinoic acid which is derived from vitamin A, and vitamin D which is synthesized in the skin in response to sunlight (see Topic K5). 

We now turn our attention to the synthesis of the fundamental lipid cholesterol. This steroid modulates the fluidity of animal cell membranes (p. 343) and is the precursor of steroid hormones such as progesterone, testosterone, estradiol, and cortisol. All 27 carbon atoms of cholesterol are derived from acetyl CoA in a three-stage synthetic process (Figure 26.6). 

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... 

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