Receptors soluble intracellular

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. 

A. Many hormones diffuse into the cell and initiate signaling by binding to soluble intracellular receptors that act as transcription factors. 

Steroid Hormones. Generally, steroid hormones arc mctaholically short-lived steroids produced in small amounts by various endocrine glands. They serve as chemical messengers that regulate a variety of physiological and metabolic activities in vertehrates. Steroid hormones bind to soluble, intracellular receptor molecules. In the nucleus of... 

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. 

Intracellular receptors include both nuclear receptors and cytoplasmic receptors, soluble proteins that are localised within the nucleoplasm and the cytoplasm, respectively. Typical ligands include the steroid hormones (e.g. testosterone, progesterone, cortisol) and derivatives of vitamins A and D, which freely diffuse through the plasma membrane. 

Following its synthesis NO, both in endothelial cells and in the adjacent smooth muscle cells, activates what has been termed its intracellular receptor, soluble guanylate cyclase. NO binds to the heme iron in the catalytic domain of the enzyme and by increasing its activity leads to an enhanced formation of cGMP (Drexler et al., 1989 Martin et al.,... 

The aryl hydrocarbon receptor (AHR), a soluble intracellular protein found in most if not all vertebrate cells and tissues, is the prototypical xenobiotic sensing receptor. The AHR is an essential component of an organism s adaptive response to xenobiotic exposure. Phylogenetic evidence indicates that the AHR may have evolved as a mechanism by which animals adapt to potential toxicants in plant food sources, but... 

Targets Intracellular (kinases) Extracellular (cell surface receptors, soluble ligands)... 

Kim D, Cavanaugh EJ (2007) Requirement of a Soluble Intracellular Factor for Activation of Transient Receptor Potential Al by Pungent Chemicals Role of Inorganic Polyphosphates. J Neurosci 27 6500—6509. 

Purinergic System. Figure 2 Schematic of sympathetic cotransmission. ATP and NA released from small granular vesicles (SGV) act on P2X and a-i receptors on smooth muscle, respectively. ATP acting on inotropic P2X receptors evokes excitatory junction potentials (EJPs), increase in intracellular calcium ([Ca2+]j) and fast contraction while occupation of metabotropic ar-adrenoceptors leads to production of inositol triphosphate (IP3), increase in [Ca2+]j and slow contraction. Neuropeptide Y (NPY) stored in large granular vesicles (LGV) acts after release both as a prejunctional inhibitory modulator of release of ATP and NA and as a postjunctional modulatory potentiator of the actions of ATP and NA. Soluble nucleotidases are released from nerve varicosities, and are also present as ectonucleotidases. (Reproduced from Burnstock G (2007) Neurotransmission, neuromodulation cotransmission. In Squire LR (ed) New encyclopaedia of neuroscience. Elsevier, The Netherlands (In Press), with permission from Elsevier). 

Cytokine receptors can be divided into two groups those whose intracellular domains exhibit intrinsic protein tyrosine kinase (PTK) activity and those whose intracellular domains are devoid of such activity. Many of the latter group of receptors, however, activate intracellular soluble PTKs upon ligand binding. 

Understanding of the intracellular localization of steroid receptors has gone through a number of phases, beginning with the view that receptors translocated from cytoplasm to nucleus in the presence of hormone. Indeed, with the exception of thyroid hormone receptors, which are exclusively nuclear in location, cell fractionation studies have revealed that in the absence of hormone, steroid receptors are extracted in the soluble or cytosolic fraction. However, when steroid is present in the cell, many occupied receptors are retained by purified cell nuclei. Histological procedures, such as immunocytochemistry, have confirmed the largely nuclear localization of occupied receptors, but... 

The intracellular distribution of steroid hormone receptors has long been the object of controversy. The first theoretical formulation on the intracellular location of the ERs was elaborated by Jensen in 1968 and is known as the two-step theory. Its execution was based entirely on biochemical observations obtained by means of tritium-marked estradiol. The ERs, in cells not exposed to hormones, are found abundantly in the soluble cell fraction, or cytosol (Fig. 1.1). Treatment with hormones confines the receptors to the particulated or nuclear fraction and causes their disappearance from the cytosol. The two-step theory established that the receptor is found in the cytoplasm naturally and upon the arrival of a hormone it is transformed into a complex hormone-receptor (first step) capable of translocating itself to the nucleus and of modifying gene expression (second step). 

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