Corticosteroids regulation

Cortisol and Other Corticosteroids Regulate a Variety of Body Processes... 

All corticosteroids have the same general mechanism of action they traverse cell membranes and bind to a specific cytoplasmic receptor. The steroid-receptor complex translocates to the cell nucleus, where it attaches to nuclear binding sites and initiates synthesis of messenger ribonucleic acid (mRNA). The novel proteins that are formed may exert a variety of effects on cellular functions. The precise mechanisms whereby the corticosteroids exert their therapeutic benefit in asthma remain unclear, although the benefit is likely to be due to several actions rather than one specific action and is related to their ability to inhibit inflammatory processes. At the molecular level, corticosteroids regulate the transcription of a number of genes, including those for several cytokines. 

CRH (Corticotropin releasing hormone) is expressed in the nucleus paraventricularis of the hypothalamus and drives the stress hormone system by activating synthesis and release of corticotropin at the pituitary and in turn corticosteroid from the adrenal cortex. CRH is also expressed at many other brain locations not involved in neuroendocrine regulation, e.g. the prefrontal cortex and the amygdala. Preclinical studies have shown that CRH also coordinates the behavioral adaptation to stress (e.g. anxiety, loss of appetite, decreased sleepiness, autonomic changes, loss of libido). 

Many factors are involved in the regulation of bone metabolism, only a few of which will be mentioned here. Some stimulate osteoblasts (eg, parathytoid hormone and 1,25-dihydroxycholecalciferol) and others inhibit them (eg, corticosteroids). Parathyroid hormone and 1,25-dihydroxycholecalciferol also stimulate osteoclasts, whereas calcitonin and estrogens inhibit them. 

F3. Feldman, D., Mondon, C. E., Homer, J. A., and Weiser, J. N Glucocorticoid and estrogen regulation of corticosteroid-binding globulin production by rat liver. Am. J. Physiol. 237, E493-E499 (1979). 

Corticosteroid receptors regulate transcription in the nervous system 464... 

The mechanisms of corticosteroid receptor regulation of transcription have been elucidated 464... 

The mechanisms of corticosteroid receptor regulation of transcription have been elucidated. Both type I and type II corticosteroid receptors are members of a superfamily of ligand-activated transcription factors defined by protein sequence similarity. Included in this superfamily are various other steroid receptors, such as the estrogen receptor, as well as members of the retinoic acid receptor... 

Corticosteroids synthesized by the adrenal gland are mineralocorticoids and GC. Min-eralocorticoids regulate fluid and electrolyte balance by affecting ion transport in the kidney. Cortisol, the primary circulating GC in most species (including humans), has many activities, including resistance to stress, regulation of intermediary metabolism, and immunosuppressive and anti-inflammatory effects. GC synthesis and secretion is... 

One class of agents which inhibits LT production in stimulated cell systems, but probably not by direct 5-LO inhibition, is the anti-inflammatory corticosteroids, represented by dexamethasone (10) [30-34]. The well-known inhibition of PG production seen with eorticosteroids is not due to direct CO inhibition, but has been attributed to the inhibition of arachidon-ic acid mobilization by phospholipase A2, caused by enhanced biosynthesis of one or more proteins called lipocortins [35] (although this hypothesis is now being seriously questioned [36]). More recent evidence indicates the possibility of down-regulation of CO enzyme levels [37-39] similar mechanisms involving altered gene regulation could be involved in the observed effects on LT production as well. 

The tenn corticosteroids refers to steroid hormones secreted by the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. 

Corticosteroids—Chemicals produced in small amounts by a group of cells that sits above the kidneys. The chemicals regulate how the body makes and breaks down sugar, fat, and protein, as well as how the body maintains its water and salt balance. Can be used as drugs. 

Glucocorticoids and mineralocorticoids are uniquely produced by the adrenal cortex, and are collectively termed corticosteroids. Apart from aldosterone, glucocorticoid secretion is regulated by the pituitary hormone, corticotrophin. The principal corticosteroids synthesized in the body are illustrated in Figure 1.6. Glucocorticoids generally exhibit weak mineralocorticoid actions and vice versa. 

Wissink S, Meijer O, Pearce D, van Der Burg B, van Der Saag PT (2000) Regulation of the rat serotonin-lA receptor gene by corticosteroids. J Biol Chem 275 1321-1326... 

GC exert their regulatory effects on the HPA system via two types of corticosteroid receptors the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) (Reul and De Kloet 1985). GRs occur everywhere in the brain but are most abundant in hypothalamic CRH neurons and pituitary corticotropes. MRs, in contrast, are highly expressed in the hippocampus and, at lower expression levels, in hypothalamic sites involved in the regulation of salt appetite and autonomic outflow. The MR binds GC with a tenfold higher affinity than does the GR (Reul and De Kloet 1985). These findings on corticosteroid receptor diversity led to the working hypothesis that the tonic influences of corticosterone... 

The corticosteroids have an array of actions in several systems that may be relevant to their effectiveness in asthma. These include inhibition of cytokine and mediator release, attenuation of mucus secretion, up-regulation of (3-adrenoceptor numbers, inhibition of IgE synthesis, attenuation of eicosanoid generation, decreased microvascular permeability, and suppression of inflammatory cell influx and inflammatory processes. The effects of the steroids take several hours to days to develop, so they cannot be used for quick relief of acute episodes of bronchospasm. 

Since the synthesis and release of cortisol are regulated by pituitary corticotrophin, removal of the pituitary gland results in decreased function and eventual atrophy of the zona fasciculata and zona reticularis. Infusion of supraphysiological concentrations of cortisol will suppress corticotrophin secretion from the pituitary and wUl markedly decrease circulating corticotrophin levels. This occurrence implies a negative feedback control for corticotrophin and corticosteroid release (Fig. 60.3). 

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. 

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