Glucocorticoids transport

Vitamin D withdrawal is an obvious treatment for D toxicity (219). However, because of the 5—7 d half-life of plasma vitamin D and 20—30 d half-life of 25-hydroxy vitamin D, it may not be immediately successful. A prompt reduction in dietary calcium is also indicated to reduce hypercalcemia. Sodium phytate can aid in reducing intestinal calcium transport. Calcitonin glucagon and glucocorticoid therapy have also been reported to reduce semm calcium resulting from D intoxication (210). 

Yates CR, Chang C, Kearbey JD, Yasuda K, Schuetz EG, Miller DD, et al. Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res 2003 20 1794-803. 

Recently, Tse et al. [73] and Orlowski et al. [74] have cloned a third isoform of Na /H exchanger (named NHE-3). The inferred 832-amino acid sequence of rabbit NHE-3 is 41% identical with NHE-1, 44% identical with NHE-2, and has a similar secondary structure. In contrast to NHE-1 and NHE-2, NHE-3 is only expressed in epithelia in intestine and kidney. Moreover, administration of glucocorticoids, which stimulates transport activity of the apical Na /H" exchanger in rabbit intestine, increased levels of NHE-3 transcripts but did not affect NHE-1 or NHE-2 [75]. Taken together, these results suggest that NHE-3 may encode a resistant-type Na /H exchanger of epithelia. A fourth Na /H exchanger isoform (NHE-4) is preferentially expressed in stomach [74]. 

The cellular mechanism of action of hydrocortisone, a glucocorticoid, is also related to proteins but not by the enhancement of cAMP production. Hydrocortisone is transported by simple diffusion across the membrane of the cell into the cytoplasm and binds to a specific receptor The steroid-receptor complex is activated and enters the nucleus, where it regulates transcription of specific gene sequences into ribonucleic acid (RNA). Eventually, messenger RNA (mRNA) is translated to form specific proteins in the cytoplasm that are involved in the steroid-induced cellular response. 

Hormones and vitamins also play a role in regulation of ASBT. Both glucocorticoid receptor ligands and co-expression of the glucocorticoid receptor gene increased activity of ASBT, while there is also evidence that dihydroxy vitamin D binds directly to the vitamin D response element and increases expression of ASBT, leading to increased transport of bile acids into the enterocyte. ... 

The phosphorylated Stat proteins form homodimeric or heterodimeric complexes and are transported as such into the nucleus (Fig. 11.7). In the nucleus, they bind to corresponding DNA elements in the promoter region of cytokine responsive genes. Stimulation of transcription takes place in cooperation with other proteins such as p300, CBP (see 1.4.6), glucocorticoid receptors and c-jim. 

Glucocorticoid hormones alter bone mineral homeostasis by antagonizing vitamin D-stimulated intestinal calcium transport, by stimulating renal calcium excretion, and by blocking bone formation. Although these observations underscore... 

Several drugs (for example amiodarone, androgens, glucocorticoids, phenytoin, and salicylates) interfere with the transport or metabolism of thyroid hormones and thereby alter thyroid function tests. These have been reviewed (90). In patients taking levothyroxine serum TSH rises after treatment with sertraline (91) and antimalarial prophylaxis with chloroquine and proguanil... 

Boehmer C., Rajamanickam J., Schniepp R., Kohler K., Wulff P., Kuhl D., Palmada M., and Lang F. (2005). Regulation of the excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent kinases SGK1 and SGK3. Biochem. Biophys. Res. Commun. 329 738-742. 

Glucocorticoids accomplish this paradox by affecting the metabolism of glucose, fat, and protein (see Figure 29-4). Cortisol facilitates the breakdown of muscle into amino acids and lipids into free fatty acids, which can be transported to the liver to form... 

The glucocorticoids work by binding to specific intracellular receptors in target tissues. The receptor hormone complex is then transported into the nucleus in which the complex interacts with the DNA, thus augmenting the synthesis of specific RNAs. 

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