Steroid transport protein

Danazol Danazol is a weak partial agonist that binds to progestin, androgen, and glucocorticoid receptors in cells and to steroid transport proteins in the blood. Danazol also inhibits several P450 enzymes involved in gonadal steroid synthesis. The drug is sometimes used in the treatment of endometriosis and fibrocystic disease of the breast. 

Testiculat androgens are synthesized in the interstitial tissue by the Leydig cells. The immediate precursor of the gonadal steroids, as for the adrenal steroids, is cholesterol. The rate-limiting step, as in the adrenal, is delivery of cholesterol to the inner membrane of the mitochondria by the transport protein StAR. Once in the proper location, cholesterol is acted upon by the side chain cleavage enzyme P450scc. The conversion of cholesterol to pregnenolone is identical in adrenal, ovary, and testis. In the latter two tissues, however, the reaction is promoted by LH rather than ACTH. 

Steroid and thyroid hormones are minimally soluble in the blood. Binding to plasma proteins renders them water soluble and facilitates their transport. Protein binding also prolongs the circulating half-life of these hormones. Because they are lipid soluble, they cross cell membranes easily. As the blood flows through the kidney, these hormones would enter cells or be... 

The most frequent protein in the plasma, at around 45 g is albumin. Due to its high concentration, it plays a crucial role in maintaining the blood s colloid osmotic pressure and represents an important amino acid reserve for the body. Albumin has binding sites for apolar substances and therefore functions as a transport protein for long-chain fatty acids, bilirubin, drugs, and some steroid hormones and vitamins. In addition, serum albumin binds Ca "" and Mg "" ions. It is the only important plasma protein that is not glycosylated. 

Albumin is the most abundant protein in human and other animal plasma. It is estimated that up to 40% of the total albumin in humans is in circulation transporting essential nutrients, especially those that are sparingly soluble in aqueous-based plasma. For example, the fatty acids, which are important fuel molecules for the peripheral tissue, are distributed by albumin. In addition, albumin is the plasma transport protein for other substances including bilirubin, thyroxine, and steroid hormones. Also, many drugs including aspirin, sulfanilamides, clofibrate, and digitalis bind to albumin and are most likely carried to their sites of action by the protein. 

Tissues contain two types of receptors for 1,25-dihydroxyvitamin D a classic steroid hormone nuclear receptor and a putative membrane receptor. 1,25-Dihydroxyvitamin D interacts with the nuclear receptor to form a receptor-ligand complex (Fig. 30-4). This complex then interacts with other nuclear proteins, such as the retinoic acid receptor (RXR) to form a functional transcription complex. The main effect of this transcription complex is to alter the amount of mRNAs coding for selected proteins such as cal-bindin, the calcium transport protein in the intestine, and the vitamin D receptor. In concert with PTH, 1,25-dihydroxyvitamin D acts to mobilize calcium from bone.As a consequence, serum calcium and phosphate homeostasis is maintained by a combination of 1,25-dihydroxyvitamin D stimulation of intestinal absorption and bone turnover. 

DNA. Steroid receptors have been reported in mitochondria (17) and cell membranes, although it is not yet clear whether all of these receptors are the same as the intracellular steroid receptors (16, 18-22 vs. 23). Some of the membrane-bound receptors for steroids are G protein-coupled receptors (24—27). A recent report suggests that membrane-bound steroid receptors can interact with, and augment the transcriptional activity of, the intracellular receptors (24). Finally, steroids can bind to nonreceptor molecules such as enzymes and transport proteins (see above), which may have yet undiscovered consequences. 

Steroid hormones (e.g., cortisol and estrogen) are hydro-phobic and insoluble in water. These hormones circulate in plasma, reversibly bound to transport proteins (e.g., cortisol-binding globulin and sex-hormone binding globulin) with only a small fraction free or unbound available to exert physiological action.The half-life of steroid hormones is 30 to 90 minutes. Free steroid hormones, being hydrophobic, enter the cell by passive diffusion and bind with intracellular receptors either in the cytoplasm or the nucleus. ... 

A generic depiction of the mechanism for steroid hormone activity at a target cell is shown in Figure 30-4. The first step consists of dissociation of the hormone from the plasma transport protein and entry into the cell by diffusion across the plasma membrane. In the second step the hormone binds with the receptors in the cytoplasm and nucleus. Receptors for glucocorticoid and aldosterone are found in the cytoplasm and receptors for estrogen and progesterone are found in the nucleus. Recall that receptors for... 

Lipophilic hormones that use intracellular gene-specific transcription factors include the steroid hormones, thyroid hormone, retinoic acid (active form of vitamin A), and vitamin D (Fig. 11.8). Because these compounds are water-insoluble, they are transported in the blood bound to serum albumin, which has a hydrophobic binding pocket, or to a more specific transport protein, such as steroid hormonebinding globulin (SHBG) and thyroid hormone-binding globulin (TBG). The intracellular receptors for these hormones are structurally similar and are referred to as the steroid hormone/thyroid hormone superfamily of receptors. 

The final step in cortisol synthesis requires transport of 11-deoxycortisol back to the inner membrane of the mitochondria, where P450cn (11-P-hydroxylase) receives electrons from electron transport protein intermediates (adrenodoxin, which when oxidized is reduced by adrenodoxin reductase). The enzyme then transfers these reducing equivalents by way of oxygen to 11-deoxycortisol for hydroxylation at Cl 1 to form cortisol. The rate of biosynthesis of cortisol and other adrenal steroids is dependent on stimulation of the adrenal cortical cells by adrenocorticotropic hormone (ACTH). 

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