Hormones and receptors

The term endocrine disrupter (ED) has tended to be used for those chemicals which act specifically at the level of the hormone receptor present in the target cells of various organs. Such chemicals may either mimic the action of the natural hormone (agonistic activity) or are sufficiently similar in molecular shape to the naturally produced hormone to interfere with the interaction between the hormone and receptor, thus blocking or impeding the activation of the receptor (antagonsitic activity). Such effects may occur at very low concentrations (as with the endogenous hormone), compared with the concentrations normally required to elicit the more traditional toxic effects attributed to chemicals. Recently,... 

Sepharose (e.g. Sepharose CL and Bio-Gel A) is a bead form of agarose gel which is useful for the fractionation of high molecular weight substances, for molecular weight determinations of large molecules (molecular weight > 5000), and for the immobilisation of enzymes, antibodies, hormones and receptors usually for affinity chromatography applications. 

Adenylyl Cyclases. Figure 4 Regulation of adenylyl cyclases by G-proteins. Abbreviations Hs, Hj, Rs, and Rj denote hormones and receptors that lead to stimulation or inhibition, respectively, of adenylyl cyclases, Ca and Ci are active and inactive configurations of adenylyl cyclase, Fo forskolin binding site, Gs and Gj are GTP-dependent regulatory proteins comprising their respective as, and (3y subunits. 

Weigent, D.A. and Blalock, J.E., Interactions between the neuroendocrine and immune system common hormones and receptors, Immunol. Rev., 100, 79, 1987. 

J. L. Carpentier, P. Gorden, A. Roberts, L. Orci (1986). Internahzation of polypeptide hormones and receptor cycling. Experientia 42 734—744. 

Cytoplasmically localized protein tyrosine phosphatases have a catalytic domain and other structural elements that specify the subcellular localization and association with effector molecules. These structural elements contain sequence signals for nuclear localization, for membrane association and for association with the cytoskeleton (see Fig. 8.16). The presence of SH2 domains suggests that these molecules might interact with signaling pathways involving growth hormones and receptor tyrosine kinases. 

The locus of the encounter between hormone and receptor may be extracellular, cytosolic, or nuclear, depending on the hormone type. The intracellular consequences of hormone-receptor interaction are of at least six general types (1) a change in membrane potential results from the opening or closing of a hormone-gated... 

Such observations have led to the idea that depression may be a pseudomonoamine deficiency due to a deficiency in signal transduction from the monoamine neurotransmitter to its postsynaptic neuron in the presence of normal amounts of neurotransmitter and receptor. If there is a deficiency in the molecular events that cascade from receptor occupancy by neurotransmitter, it could lead to a deficient cellular response and thus be a form of pseudomonoamine deficiency (i.e., the receptor and the neurotransmitter are normal, but the transduction of the signal from neurotransmitter to its receptor is somehow flawed). Such a deficiency in molecular functioning has been described for certain endocrine diseases such as hypoparathyroidism (parathyroid hormone deficiency), pseudohypoparathyroidism (parathyroid receptors deficient but parathyroid hormone levels normal), and pseudo-pseudohypoparathyroidism (signal transduction deficiency leading to hypoparathyroid clinical state despite normal levels of hormone and receptor). 

Cytosolic Hormone Receptors. Steroid hormones typically bind to protein receptors, which are located directly within the cytosol (see Fig. 28-2).17 Of course, this means that the hormone must first enter the cell, which is easily accomplished by the steroid hormones because they are highly lipid soluble. After entering the cell, the hormone initiates a series of events that are depicted in Figure 28-3. Basically, the hormone and receptor form a large activated steroid-receptor complex.17 This complex travels to the cell s nucleus, where it binds to specific genes located within the DNA sequence.31,40 This process initiates gene expres-... 

Kulinsky, V.I. and Olkhovsky, LA. (1992). Two alternative strategies - resistance and tolerance - developing under unfavourable conditions. Role of hormones and receptors (In Russian). Uspekhi Sovremennoy Biologii 112,697-714. 

It should be pointed out, however, that not all hormones dissociate from their receptor in the pH 5.5 environment of the endosome [24], Some hormone-receptor complexes require much lower pH values for dissociation to occur. Although not a peptide hormone, the iron-transport protein transferrin is a peculiar example of this phenomenon and should be pointed out. In this case, at the neutral pH of the extracellular fluid transferrin containing bound iron binds to its cell surface receptor and is internalized. In the low pH environment of the endosome, iron becomes dissociated from transferrin, but transferrin remains bound to its receptor. The transferrin receptor, with bound transferrin, is then recycled to the cell surface. With iron no longer bound to the transferrin, the transferrin readily dissociates from its receptor at the neutral pH of the extracellular fluid [25,26]. This mechanism provides for an efficient continual uptake of iron into cells. Unlike transferrin, however, in those instances where peptide hormones have been documented not to be dissociated from their receptor in the endosome compartment, the hormone and receptor are delivered to the lysosomes via fusion of the endosomes with lyso-somes, where both hormone and receptor are degraded [24,27]. The continuous degradation of the receptor with each round of RME eventually leads to a decrease in the number of receptors on the cell surface, a phenomenon called down-regulation. 

THE STRUCTURAL BASIS FOR BIOLOGICAL SIGNALING, REGULATION, AND SPECIFICITY IN THE GROWTH HORMONE-PROLACTIN SYSTEM OF HORMONES AND RECEPTORS... 

A clear introduction to the mechanisms of hormonal function and disruption has been provided by Eubanks (1997) and is summarized here. Hormones are regulatory molecules produced by the endocrine system that fit precisely to proteins called receptors. This interaction is very precise and constitutes the reception of a chemical message by a particular cell. Upon reception of the message, dramatic changes can occur in the cell although extremely small amounts of the hormone may be present. The reaction to the interaction of the hormone and receptor are specific to the type of cell... 

Miller LJ. Gastrointestinal hormones and receptors. In Yamada T, ed. Textbook of gastroenterology, 4th ed. Philadelphia Lippincott Williams and Wilkins, 2003 48-77. 

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