Steroid hormone binding proteins

Cadmium is a divalent metal ion. It is a toxic metal ion that can induce damage to the reproductive system. In general, cadmium can bind to sites of proteins that are normally used to bind zinc, (t is possible that the cadmium-induced damage to the reproductive system results from the binding to the zinc fingers of the steroid hormone-binding proteins. 

Steroid hormone binding proteins, 393 Steroid hormones, 807 synthesis, 747 r.tnc fingers and, 805 Sterol response elemenl, 367-368 Sterol response element binding protein (SREBF), 367-368 Stctichiometry, 275 Stomach... 

Liquid-liquid partition chromatography techniques based on aqueous-aqueous systems have successfully been employed in the fractionation of crude human serum, purification of steroid hormone-binding proteins from human serum, isolation of basic proteins from crude bacterial extracts, purification of immunoglobulins and monoclonal antibodies, DNA fractionations by size, topology and base sequence, as well as the isolation of soluble and ribosomal RNAs in preparative amounts from bulky mixtures [10]. Highspeed CCC using PEG-dextran system has also been employed in the separation of proteins [6]. 

The Gla-containing proteins of the blood coagulation system are all modular with the Gla-domain N terminal. Factors VII, IX, and X and protein C form a group with the same domain structure. The Gla domain is followed by two EGF-like domains, of which the first one also binds calcium (see Section IV.C), and a serine protease domain, also with a calcium-binding site (see Section IV.D). Prothrombin and protein S have somewhat different domain structures (145, 146). In prothrombin the Gla domain is followed by a hexapeptide with a disulfide loop, two kringle domains, and the C-terminal serine protease domain. In protein S the Gla domain is followed by the thrombin-sensitive loop, four EGF-like domains, and the C-terminal domain that is homologous to plasma steroid hormone-binding proteins. 

Wingfield, J.C., Matt, K.S. Famer, D.S. (1984). Physiological properties of steroid hormone binding proteins in avian blood. Gm. Comp. Endocrinol, 53, 281-92. 

The increased levels of estradiol stimulate the biosynthesis of the steroid hormone binding protein. The reduction of estriol formation in liver cirrhosis is likely to result in part from cholestasis which interrupts the enterohepatic circulation and in more severe cases from poor uptake of estrogens by the hepatic cells, thus preventing the conversion of estrogen to estriol. 

There are also numerous enzymes anchored in membranes of the microsomal cell fraction that participate in the metabolism of steroid hormones. Thus, those of the p450 family, which carry out molecular oxidation, or the sulfatases and sulfotransferases, more or less specific to several hormones (Pasqualini et al. 1995). The affinity of steroid hormones for proteins of the membrane (Kd between 10 and 100 nM) is frequently greater than that which some of these enzymes present for their substrates (Luzardo et al. 2000). Therefore, it is unlikely that a part of the proteins of the membrane that bind steroids is in reality enzymes metabolizing these hormones. 

An account of the principles which help to understand how hormones achieve their roles in the body is given in Chapter 12. The understanding is based on separation of the effects of hormones into three components the action, the effects (biochemical and physiological) and the function. A steroid hormone binds to a cytosolic intracellular receptor, which then moves into the nucleus where it binds to DNA at a specific site (the steroid response element) and activates genes which result in the formation of proteins that elicit biochemical and physiological effects. This is discussed for cortisol in Chapter 12 and aldosterone in Chapter 22. Much of the interest in the reproductive steroid hormones is in the physiological effects and how these account for their functions. 

Figure 17.4 Intracellular steroid receptor activation by hormone ligands, (a) Steroid hormones diffuse across the cell membrane into the cell. (b) Steroid hormone receptors in the basal state bound to accessory proteins, (c) Steroid hormones bind to receptors and accessory proteins are dissociated from the receptors. (d) Hormone receptor complexes dimerize. (e) Dimer complexes enter the nucleus and initiate transcription of responsive genes.

All classes of steroid hormones bind to specific cytoplasmic receptors in their respective target tissues, and are then translocated to the nucleus. For example, testosterone, a lipid-soluble substance, enters the cell and is enzymatically reduced to dihydrotestosterone by 5-a reductase. Dihydrotestosterone then becomes bound to a specific androgen receptor site located in the cytoplasm. This complex becomes activated and is then translocated to the nucleus, where it binds to the chromatin acceptor site consisting of DNA and nonhistone chromosomal proteins. This interaction results in the transcription of a specific messenger RNA that is then relocated to the cytoplasm and translated on the cytoplasmic ribosomes, resulting in the synthesis of a new protein that sponsors the androgenic functions (Figure 61.6). 

Lipid-soluble hormones act usually by gene activation/deactivation. Examples of these hormones include steroids, thyroid hormone, and vitamin A (retinoic acid). The hormones are transported through the circulation in association with a hormone-binding protein and are soluble in the plasma membrane of the cell. Their receptors are intracellular, and they act on gene transcription (the synthesis of messenger RNA) rather than at the protein level. Thus, they act more slowly than do the soluble hormones, on the scale of days rather than minutes. 

The steroid hormones are hydrophobic, this property enabling them to readily cross the plasma membrane to bind their respective cytosolic receptors. However, transport of such hydrophobic hormones through the blood stream requires hormone-binding proteins such as the steroid-binding globulins and corticosteroid-binding globulins. 

Calcitriol acts like a steroid hormone, binding to, and activating, nuclear receptors that modulate gene expression. More than 50 genes are known to be regulated by calcitriol (see Table 3.3), but vitamin D response elements have only been identified in a relatively small number, including calcidiol 1-hydroxylase and 24-hydroxylase calbindin, a calcium binding protein in the... 

Hormone transport. Steroid hormones bind to carrier proteins and are transported in the blood stream to their required sites. At these sites, the hormones transfer to storage sites while they await release for use. When these carrier proteins are interfered with, the hormones are not delivered to the required sites. 

Steroid hormones perform many functions in cells, one of which is to activate gene expression by binding to steroid receptors, proteins in the cytoplasm that, when activated, act as factors that initiate transcription. All steroid hormones are derived from cholesterol and, as a result, have similar chemical structures. Steroid hormones differ one from another primarily in hydrox-ylation of particular carbon atoms and by aromatiza-tion of the steroid A ring of the molecule. Once a steroid hormone binds to a steroid receptor protein, the complex undergoes a series of structural changes that result in the complex binding to DNA at a particular sequence called a steroid response element (SRE)... 

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