Steroid hormones transport

We turn now to the biosynthesis of lipid structures. We begin with a discussion of the biosynthesis of fatty acids, stressing the basic pathways, additional means of elongation, mechanisms for the introduction of double bonds, and regulation of fatty acid synthesis. Sections then follow on the biosynthesis of glyc-erophospholipids, sphingolipids, eicosanoids, and cholesterol. The transport of lipids through the body in lipoprotein complexes is described, and the chapter closes with discussions of the biosynthesis of bile salts and steroid hormones. 

The breast cancer resistance protein (BCRP) belongs to the G-branch of the ABC-transporter family (ABCG2). In contrast to most other ABC-proteins, BCRP consists of only one transmembrane domain (TDM) with one nucleotide binding fold (NBF) at its C-terminus. Because of this structural characteristic BCRP as well as other ABC-transporters with only one TMD are termed half transporters. To achieve functional activity these transporters have to form hetero- or homodimers. BCRP is involved in the multidrug resistance of certain tumors and transports endogenous compounds like cholesterol and steroid hormones. 

H)2-D3 is produced by a complex series of enzymatic reactions that involve the plasma transport of precursor molecules to a number of different tissues (Figure 42-9). One of these precursors is vitamin D—really not a vitamin, but this common name persists. The active molecule, l,25(OH)2-D3, is transported to other organs where it activates biologic processes in a manner similar to that employed by the steroid hormones. 

Gonadal Steroids Are Transported by Sex Hormone-Binding Globulin... 

Another important function of albumin is its ability to bind various ligands. These include free fatty acids (FFA), calcium, certain steroid hormones, bilirubin, and some of the plasma tryptophan. In addition, albumin appears to play an important role in transport of copper in the human body (see below). A vatiety of drugs, including sulfonamides, penicilhn G, dicumarol, and aspirin, are bound to albumin this finding has important pharmacologic implications. 

Steroid hormones are produced by the adrenal cortex, testes, ovaries, and placenta. Synthesized from cholesterol, these hormones are lipid soluble therefore, they cross cell membranes readily and bind to receptors found intracellularly. However, because their lipid solubility renders them insoluble in blood, these hormones are transported in the blood bound to proteins. Furthermore, steroid hormones are not typically preformed and stored for future use within the endocrine gland. Because they are lipid soluble, they could diffuse out of the cells and physiological regulation of their release would not be possible. Finally, steroid hormones are absorbed easily by the gastrointestinal tract and therefore may be administered orally. 

Amine hormones include the thyroid hormones and the catecholamines. The thyroid hormones tend to be biologically similar to the steroid hormones. They are mainly insoluble in the blood and are transported predominantly (>99%) bound to proteins. As such, these hormones have longer half-lives (triiodothyronine, t3, = 24 h thyroxine, T4, = 7 days). Furthermore, thyroid hormones cross cell membranes to bind with intracellular receptors and may be administered orally (e.g., synthryoid). In contrast to steroid hormones, however, thyroid hormones have the unique property of being stored extra-cellularly in the thyroid gland as part of the thyroglobulin molecule. 

L. M., Feng, B., Giacomini, K. M., Functional characteristics and steroid hormone-mediated regulation of an organic cation transporter in Madin-Darby Canine Kidney cells, J. Pharmacol. Exp. Ther. 2001, 299, 392— 398. 

In addition to its osmoregulatory function, HSA serves a transport function. Various metabolites travel throughout the vascular system predominantly bound to HSA. These include fatty acids, amino acids, steroid hormones and heavy metals (e.g. copper and zinc), as well as many drugs. 

The entrance of steroid hormones into the cells has always been assumed to be a passive phenomenon, based on its solubility in the phospholipids of the cell membrane. Nevertheless, the existence of specific fixation of steroid hormones to cell membranes has opened the possibility of their entrance into the cells mediated by proteins of the membrane (Levin 2002). Nevertheless, it has not been possible to verify that they participate in some way in the transportation of steroids to the interior of the cell (Beato et al. 1996 Beato 1989). For them, other possible extragenomic actions have been postulated such as enzymes that participate in the metabolism of hormones or even membrane receptors (Beato et al. 1996 Chirino et al. 1991 Fernandez et al. 1994 Gruber et al. 2002 Revelli et al. 1998). 

The normal LDL-receptor is used to transport cholesterol into cells when it is required, for example, in the formation of membranes or synthesis of steroid hormones. The number of these receptors is regulated by the intracellular level of cholesterol the higher the level, the lower is the... 

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. 

Transport of thyroxin and triiodothyronin Maintenance of osmotic pressure transport of fatty acids, bilirubin, bile acids, steroid hormones, pharmaceuticals and inorganic ions. 

The steroid hormone aldosterone (see p. 55) increases Na reuptake, particularly in the distal tubule, while atrial natriuretic peptide (ANP) originating from the cardiac atrium reduces it. Among other effects, aldosterone induces Na /K" ATPase and various Na" transporters on the luminal side of the cells. 

Lipophilic hormones, which include steroid hormones, iodothyronines, and retinoic acid, are relatively small molecules (300-800 Da) that are poorly soluble in aqueous media. With the exception of the iodothyronines, they are not stored by hormone-forming cells, but are released immediately after being synthesized. During transport in the blood, they are bound to specific carriers. Via intracellular receptors, they mainly act on transcription (see p. 358). Other effects of steroid hormones—e.g., on the immune system—are not based on transcriptional control. Their details have not yet been explained. 

Das B.S., L.S. Lee, P.S.C. Rao, and R.P. Hultgren (2004). Sorption and degradation of steroid hormones in soils during transport Colunm studies and model evaluation. Environmental... 

Many receptors have been identified in aU cases they are proteins. Some of the proteins have enzymatic activity. Some receptors serve as transport vehicles across the cellular membranes, as is the case with the receptors for steroid hormones (Baxter and Forsham, 1972). 

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