The adrenal hormones

A somewhat related sequence leads to trilostane (111), a compound that inhibits the adrenal gland more specifically the agent blocks some of the metabolic responses elicited by the adrenal hormone ACTH in experimental animals. Reaction of the hydroxy-methylene derivative 108, obtained from testosterone, with hydroxylamine gives the corresponding isoxazole (109). Oxidation of the C-4,5 double bond by means... 

Variation in different strains of mice to X radiation has recently been studied.46 The percentage depression of growth (below the controls) produced by radiation of different strains was as follows Z, 24 per cent RI, 27 per cent S, 35 per cent E, 59 per cent LWG, 85 per cent, BALB/GW, 161 per cent. Heavier strains tended to be more resistant, and females were more resistant than males. In another study, a 4-fold decrease in head sensitivity (to radiation) was observed, in the following order dba, Marsh, C57 black, and C3H. Sensitivity seems to be related to the adrenal hormones.47... 

Serum levels of the adrenal hormones corticosterone B, dehydroepiandrosterone, and dehydro-... 

Norephedrine and ephedrine mimic and stimulate the release of the adrenal hormones norepinephrine and epinephrine. Norephinephrine raises heart rate and epinephrine stimulates carbohydrate metabolism resulting in an increased metabolic rate, fatty acids release from lipocytes (fat cells), and a protein sparing effect. Caffeine simply prolongs the effect. 

Cholesterol also serves as a precursor to other important molecules. Bile acids aid in lipid absorption during digestion. Steroid hormones all derive from cholesterol, including the adrenal hormones that maintain fluid balance Vitamin D, which is an important regulator of calcium status and the male and female sex hormones. Although humans wouldn t survive in one sense or another without cholesterol metabolites, cholesterol brings with it some well-known side effects. Doctors find cholesterol derivatives, being essentially insoluble in water, in the deposits (plaque) that characterize diseased arteries. 

Adrenocorticotropic hormone (Fig. 4) stimulates the cells of the adrenal cortex into the secretion and production of steroid hormones. Conversely, the pituitary secretion of ACTH is inhibited by the adrenal hormones via a feedback mechanism. 

Two types of human hormone are steroidal—the sex hormones such as oestradiol and testosterone and the adrenal hormones such as cortisone. Cholesterol is a steroid too, as is vitamin D, derived from ergosterol. 

Steroids A large family of drugs related to the adrenal hormone cortisone. They include anabolic steroids and corticosteroids. 

The adrenal hormone (-yadrenaline was the first hormone isolated and the first synthesized. Its structure was proved by the following synthesis ... 

All tissues of the body contain potassium. It is found mainly in the muscle followed by the skeleton. Excretion of potassium via urine is also controlled by hemostatic mechanisms the kidney regulates this so that there is normally no major loss of this essential element. The amount of potassium excreted depends on the chloride ion concentration and the adrenal hormone secretion level. 

Sodium is freely filtered by the glomeruli. Seventy to 80% of the filtered Na" load is then actively reabsorbed in the proximal tubules, with 01 and water passively following in an isoosmotic and electrically neutral manner. Another 20% to 25% is reabsorbed in the loop of Henle along with Cl" and more water. In the distal tubules, interaction of the adrenal hormone aldosterone with the coupled Na -K and Na -H exchange systems directly results in the reabsorption of Nah and indirectly of d , from the remaining 5% to 10% of the filtered load. It is the regulation of this latter fraction of filtered Na that primarily determines the amount of Na excreted in the urine. These processes are discussed in detail in Chapter 45. 

Phenylalanine and tyrosine are also metabolized in higher organisms by two routes which are quantitatively less important but physiologically of the highest importance. The first leads to the adrenal hormones adrenaline (epinephrine) and noradrenaline (norepinephrine),which may be formed as in diagram 11 this pathway also leads to melanin (diagram 12). The second leads to the thyroid hormones thyroxine and triiodothyronine, the synthesis and breakdown of which are also discussed. 

The answer is b. (Murray, pp 307-346. Scriver, pp 1667-1724. Sack, pp 121-138. Wilson, pp 287-317.) Two of the major hormones are derived from the amino acid tyrosine the adrenal hormone epinephrine and the thyroid hormone thyroxine (tetraiodothyronine). Epinephrine is the cata-... 

Catecholamines. The peripheral aspects of NE and EP as neurotransmitters were considered in Chapter 9. NE exists at significant levels in the hypothalamus and in lesser amounts in the medulla oblongata, midbrain areas, and the pons. EP, the adrenal hormone, may possibly have some central transmitter functions. DA, however, has major involvement in central mechanisms and will be considered further here. 

Experiments of this type are subject to several intrinsic difficulties which Winters discusses in some detail. Adrenal function can be assayed by physiological responses of this type only if the tissue on which the adrenal hormone acts is functioning normally. Owing to the critical role of coenzyme A in intermediary metabolism, the maintenance of normal function in any tissue during severe pantothenate deficiency is doubtful. However, experiments attempting to define adrenocortical function by studies of carbohydrate metabolism in situations of severe pantothenate deficiency are partially justified by the finding of Olson and Kaplan (1948) that in the rat the adrenal cortex suffers an earlier depletion of coenzyme A than does the liver. After 3 weeks of pantothenate deficiency, coenzyme A was significantly decreased in the adrenal and heart, whereas it was still at normal levels in the liver and kidney. After 6 weeks on the... 

There is some evidence that the adrenal hormones may exert a direct effect on fatty acid oxidation. The rate of ketone body production from octanoic acid by mouse liver slices was decreased by adrenalectomy and restored to normal by cortisone (Lipsett and Moore, 1951, 1952). Studies of the oxygen utilized per mole of octanoate disappearing led to the suggestion that the defect in fat metabolism in adrenalectomy precedes the condensation of acetyl-CoA to acetoacetate. This suggestion is consistent with the observation that adrenalectomy did not influence the rate of in vivo acetylation reactions by the rat (Dumm and Ralli, 1951). 

The influence of the adrenal hormones and of insulin on the metabolism of pyruvate and glucose by rat diaphragm muscle has been studied by Villee et al. (1952), who proposed (1) that the adrenal hormones inhibit hexokinase, as postulated by Colowick et al. (1947) (2) that the absence of the adrenals inhibited the conversion of glucose-6-phosphate to glycogen and (3) that some step in the condensation of pyruvate with oxaloacetate was accelerated by insulin and retarded by the adrenal hormones. The latter point was based in part on the observation that, in muscle from adrenalectomized rats, lactic acid production was decreased and the oxidation of pyruvate to CO2 was increased. All these suggestions... 

In studies on the role of the adrenal hormones in amino acid metabolism, cortisone has been reported to inhibit the incorporation of glycine and alanine into liver proteins and to increase the catabolism of glycine (Clark, 1950 Sinex, 1951 Barton, 1951). Proline oxidation by kidney homogenates was depressed by adrenalectomy and restored to normal by cortisone (Umbreit and Tonhazy, 1951a, 1951b). 

Experiments on the role of the adrenal hormones in fat metabolism have suggested that the cortical hormones exert a direct effect on fatty acid oxidation preceding the formation of acetyl-CoA (Lipsett and Moore, 1952). Neither the acetylation of aromatic amines (Dumm and Ralli, 1951) nor the formation of ketone bodies from pyruvate in a malonate blocked system (Lipsett and Moore, 1952) were influenced by adrenalectomy. 

Lipids have a variety of functions in living organisms. Fats and oils are a convenient and concentrated means of storing food energy in plants and animals. Phospholipids and sterols, such as cholesterol, are major components of cell membranes see upid bilayer). Waxes provide vitai waterproofing for body surfaces. Terpenes include tamins A, E, and K, and phytol (a component of chlorophyll) and occur in essential oils, such as menthol and camphor. Steroids include the adrenal hormones, sex hormones, and bile acids. 

It appears there are two main reasons for the accumulation of cholesterol esters in rats that are fed HEAR oil or erucic acid containing diets. First, the cholesterol ester hydrolase fails to increase in activity when these rats are stressed, while in control rats, when stressed, the enzyme doubles its activity (Beckett and Boyd, 1975). Second, cholesteryl erucate, which accumulates in the adrenals of rats fed HEAR oil, is only slowly hydrolyzed by the enzyme, i.e., at 25-30% of the rate of cholesteryl oleate. This may be very significant, since there is considerable cholesteryl erucate accumulation in the adrenal glands of rats fed diets high in erucic acid, i.e., this ester may constitute 29-35% of the total (Carroll, 1962 Walker and Carney, 1971). In addition, in these rats there was an accumulation of 8% cholesteryl eicose-noate. In agreement with this evidence of impaired adrenal function, the results indicate that plasma levels of one of the adrenal hormones, corticosterone, are lower in these rats than in control rats when exposed to an environmental stress (Walker and Carney, 1971 Budzynska-Topolowska eta/., 1975). 

Hydroxylation. For a time some interest was attached to the search for an 18-hydroxylator. After Reichstein and co-workers showed that aldosterone, one of the adrenal hormones regulating salt metabolism in the human, was substituted at the... 

Histochemical techniques have been used to identify the adrenal hormones. Such investigations include the use of lipid staining for cholesterol and neutral fat, and staining of aldehyde groups with SchifPs sulfur... 

The steroids include such biologically important compounds as the sterols, the bile acids, the adrenal hormones and the sex hormones. They have a common structural imit of a phenanthrene nucleus linked to a cyclopentane ring (Fig. 3.3). 

These include the female sex hormones (oestrogens), the male sex hormones (androgens) and progesterone, as well as cortisol, aldosterone and corticosterone, which are produced in the adrenal cortex. The adrenal hormones have an important role in the control of glucose and fat metabolism. 

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