Corticoid Metabolic effects

Production Site Adrenal medulla and chromaffin cells in gut Metabolic effects increases oxygen consumption. temperature, basal metabolic rate, gluconeogenesis Pituitary effects stimulates production and release of ACTH and corticoids ... 

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

Corticosteroids also affect adrenomeduUary function by increasing epinephrine production the mechanism is exertion of a stimulatory action on two of the enzymes that regulate catecholamine synthesis, tyrosine hydroxylase, the rate-Umiting enzyme, and phenyl-ethanolamine Af-methyltransferase, which catalyzes the conversion of norepinephrine to epinephrine. Steroids also influence the metabolism of circulating catecholamines by inhibiting their uptake from the circulation by noimeuronal tissues (i.e., extraneuronal uptake see Chapter 9). This effect of corticoids may explain their permissive action in potentiating the hemodynamic effects of circulating catecholamines. 

It is interesting to note that a number of researchers have attempted, more or less successfully, to construct reliable mathematical models which combine structural elements and experimental data to predict the toxicities of new substances not yet experimentally tested for humans and other species.110152 Furthermore pharmacology, toxicity, metabolism and enzyme-inhibiting effects of fluorine-containing aromatic systems (e.g., anilines, ben-zothiadiazines, butyrophenones, corticoids, phenothiazines, steroids, uracils) have been discussed in depth in the literature.153-156... 

The effects of injury and corticoid administration on protein metabolism differ significantly in animals. The content of liver nitrogen is increased by giving cortisone to rats but fracture of the femur does not have this effect in spite of increased levels of cortisol in the blood (M13). The administration of cortisone has a constant effect on nitrogen balance at all levels of nitrogen intake whereas the catabolic response to injury is reduced or even abolished by diminished protein intake and weight loss prior to injury (M12). 

Distinction between the effects of injury on protein metabolism and the effects of corticoid on protein metabolism has been made by Munro (M17, MIS) who has found a marked gain in liver nitrogen content following cortisone administration to the rat, but not after femur fracture. He also notes that cortisone has a constant action on nitrogen balance at all levels of protein intake whereas the effect of injury is obliterated by prior protein depletion. 

Triterpenes are widely distributed in plants, and in many cases are the principles responsible for their anti-inflammatory effects. Many of these compounds are active in different in vivo experimental models such as hind paw edema induced by carrageenan, serotonin and phospholipase A2 ear edema induced by phorbol and daphnane esters, ethylphenylpropiolate, arachidonic acid and capsaicin adjuvant arthritis and experimental models of allergy. Other effects have been studied in vitro, and some triterpenes are active against inflammatory enzymes like 5-lipoxygenase, elastase and phospholipase A2. Others inhibit histamine, collagenase and interleukin release, lipid peroxidation and free radical-mediated processes, metabolism of endogenous corticoids, and complement and protein-kinase activities. 

EIahn TJ, EIalstead LR, Teitelbaum SL and EIahn BH (1979) Altered mineral metabolism in uco-corticoid-induced osteopenia. Effect of 25-hydroxy-vitamin D administration. J Clin Invest 64 655 — 665. 

These are corticoids that are active in protidic and glucidic metabolism. The natural glucocorticoids are cortisone and hydrocortisone (or cortisol). The latter responds to stress by raising the level of sugar in the blood. Cortisone is used as an anti-inflammatory. Synthetic glucocorticoids have enhanced activity to permit more effective anti-inflammatory behavior and their mineralocorticoid effects are reduced. 

Corticoids being lipophilic in nature permeate the skin by passive diffusion, the rate of which is directly related to the extracellular concentration. The extracellular concentration is determined by many factors, which include the concentration of the applied steroid, percutaneous penetration, metabolic inactivation, and removal into the systemic circulation. Even though the precise sequence of cellular and subcellular events leading to the observed effects of topical steroids are still unclear these compounds are known to act in four ways anti-inflammatory, immunosupprossive, antimitotic and vasoconstrictive. 

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. 

Effect on Lipid Metabolism. Our knowledge of the effect of cortisone on lipid metabolism is still fragmentary. Interpretation of the results is complicated by the fact that the effect of the hormone seems to vary depending upon the source of the adipose tissue. Adrenalectomy stimulates and corticoid injections decrease lipogenesis in the adipose tissue of the mesentery. The decreased lipogenesis induced by corticosteroids is accompanied by release of free fatty acids. When corticosterone and hydrocortisone are added to epididymal adipose tissue incubated in vitro, the hormones fail to stimulate lipogenesis from [ " Cjpyruvate, but they accelerate fatty acid release, and the lipolytic effect is completetly blocked by actinomycin D. Consequently, one effect of glucocorticoids on some of the adipose tissues seems to be to accentuate lipid catabolism. 

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. 

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