Corticoid hormones

Sterols are widely distributed in both plants and animals. Many are of vital importance to animal physiology, such as cholesterol, the bile acids, vitamin D, sex hormones, and corticoid hormones. Many have value as medic-inals, such as the cardiac glycosides, hormones, and steroidal antibiotics. The occurrence and physiological properties of representative steroids are included in Table 30-2. 

A wide variety of compounds containing the basic 1-pyrindine skeleton have found applications in the biomedical field.50-52, 102 Compounds 52 and 53 described above, possess valuable biological activities similar to mepyrapone which has been found to act as a specific 1 l-j8-hydroxylase inhibitor in the biosynthesis of corticoid hormones in man as well as in animals.51 Antishock activity has been found in a series of octahydro- and decahydrobenzo[a]cyclopenta[/]quinolizenes (12) and (13).151tt The cardiovascular and potent antishock properties of 2,3,3a,5,6,ll,12,12a-octahydro-8-hydroxy-l/7-benzo[a]cyclopenta[/]-quinolizinium bromide (12a),151b as well as its positive inotropic effect on the cat papillary muscle preparation,1510 have been reported. Methods of synthesis for a series of these compounds and tests of their relative antishock activity have been described.151 Although some compounds were active, comparison of these results pointed up the lack of structure-activity relationships in the seven compounds tested. 

De Nicola AF, Ferrini M, Gonzalez SL, Gonzalez Deniselle MC, Grille CA, Piroli G, Saravia F, de Kloet ER (1998) Regulation of gene expression by corticoid hormones in the brain and spinal cord. J Steroid Biochem Mol Biol 65 253-272. 

Of the more recently introduced antirheumatics, indomethacin is equally active in anti-inflammatory test in intact and adrenalectomized rats , and there is no evidence of adrenal/dependence or corticoid hormone effects for flufenamic acid at non-toxic [Pg.123]

Potassium-sparing diuretics act primarily in the collecting distal duct renal tubules to promote sodium and water excretion and potassium retention. The drugs interfere with the sodium-potassium pump that is controlled by mineralo-corticoid hormone aldosterone (sodium retained and potassium excreted). Potassium is reabsorbed and sodium is excreted. 

Anatomical Considerations 458 Histophysiology 459 Adrenocortical Hormones 460 Steroid Hormone Biosynthesis Metabolic Effects of Corticoid Hormones Properties of ACTH Cushing s Syndrome... 

These war efforts led to the discovery of two major groups of corticoid hormones, the glucocorticoid and the mineralocorticoid hormones. The most active glucocorticoids are cortisone and cortisol. Both these hormones have anti-insulin effects but are without marked effect on sodium retention. Quite to the contrary, they may stimulate sodium and chloride excretion. Aldosterone has only mild corticoid effects, but it has a marked ability to influence the kidney to retain sodium. 17a-Hydroxy deoxycorticosterone, 19-hy-... 

Studies in which adrenal glands were perfused with steroids of known structure have established that 21-hydroxypregnenolone and deoxycorticosterone could serve as corticosterone precursors. 21-Deoxycortisol and lljS-hydroxyprogesterone are converted to cortisone and corticosterone, in contrast to 17a-hydroxy-progesterone, which can be converted only to cortisol. On the basis of such studies, a number of alternative pathways for glucocorticoid steroidogenesis have been described. The conversion of progesterone to corticoid hormone is shown in Fig. 8-12. 

Effect on Protein Metabolism, Corticoid hormones affect various steps of protein metabolism amino acid penetration in the cells, intracellular biosynthesis of amino acids from small precursors, protein synthesis, and protein catabolism. In discussing the effect of corticoid hormones on protein synthesis, it is necessary to distinguish between the effects of the glucocorticoid on muscle and liver. The injection of Cl 1-oxygenated corticosteroid increases the excretion of urinary nitrogen, with loss of tissue nitrogen (e.g., in heart and kidney) [51]. 

Among the unsolved problems raised by the effect of cortisone is its site of action. It is not clear whether or not cortisone acts on peripheral tissue in vivo. Corticoid hormones have little or no effect on glucose usage or protein metabolism in eviscerated animals. 

When corticosteroids are administered to animals starved for 48-72 hours, a paradoxical effect is observed. In spite of an increase in carbohydrate storage in the liver, muscle, and body fluid, the new glucose made available by the hormone is not used for oxidation. This observation suggests that corticoid hormones depress glucose utilization. Such findings are difficult to reconcile with the effects of cortisone and adrenalectomy on phosphorylase, phosphoglucomu-tase, and phosphohexose isomerase activity. The activities of these three enzymes are depressed by adrenalectomy, but are normalized by cortisone administration. 

AsWore has proposed that the primary effect of corticoid hormones is on glycogen synthesis from glu-cose-6-phosphate, rather than on glucose usage... 

Clinical examination of patients injected with corticoid hormones or afflicted with corticosteroid hypersecretion reveals that the effect of corticosteroids on lipid metabolism cannot be simple. Excess corticosteroids are responsible for abnormal lipid distribution in some parts of the adipose tissue (cheek, subclavicu-lar, and thoracic pads), which explains the development of the moon-shaped face and the buffalo hump so typical of hypercorticosteroidism. 

The mitotic reaction induced by corticoid hormone administration does not result from direct response of the tissues to corticoid hormones, but it constitutes a compensatory hyperplasia that follows the massive necrosis. 

Stimulation of erythropoiesis under the influence of glucocorticoid is demonstrated by the existence of polycythemia in patients with Cushing s disease or in individuals repeatedly injected with corticoid hormones. The mechanism of this stimulation is not known. 

In Addison s disease, secretion of all corticoid hormones formed in the adrenal cortex is markedly reduced. The lack of aldosterone is responsible for the major electrolyte imbalance—a massive loss of sodium through the kidney, salivary glands, sweat glands, and the gastrointestinal tract. The sodium loss is accompanied by a loss of water, and dehydration and its symptoms develop. The reduction in the water of the extracellular space leads to reduced renal blood flow and reduced glomerular filtration. The changes in renal physiology may lead to azotemia. 

Gallagher and co-workers [389] have emphasized that metabolites of corticoid hormones are not simply inactive end-products of a spent hormone ready for elimination, but may have their own important metabohc functions. Thus, androsterone, an end-metabohte of androgens, is an effective endogenous hypocholesterolemic hormone. Moreover, the production of androsterone is increased as one of the results of thyroxine action hence, this androgen meta-... 

About 20% of the population of the United States has cholesterol levels that exceed the recommended total. Typical adults have about 150 g in their body and for a good reason—cholesterol is vital for the mnning of the body. It is an essential building block of cell membranes, especially of the nervous system, the brain, and the spinal cord. It is also a key chemical intermediate in the biological production of other steroids, especially the sex and the corticoid hormones, including cortisone. We need cholesterol to produce bile acids, which in turn are key chemicals that help digest the fats we consume, and we need it to form vitamin D, which enables us to utilize calcium in bone construction. 

The physiological effect of corticotropin consists in the stimulation of the adrenal cortex. The production of corticoid hormones is enhanced, and stored cholesterol is... 

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