Receptor steroid

Bresnick, E.H., Sanchez, E.R., Pran, W.B. (1988). Relationship between glucocorticoid receptor steroid binding capacity and association of the Mr 90.000 heat shock protein with the unliganded receptor. J. Steroid Biochem. 30,267-269. 

Movement to intracellular receptors (steroid hormones a form of diffusion)... 

Levin ER (2002) Cellular functions of plasma membrane estrogen receptors. Steroids 67 471... 

F. Wust, K.E. Carlson, J.A. Katzenellenbogen, Synthesis of novel arylpyrazolo corticosteroids as potential ligands for imaging brain glucocorticoid receptors. Steroids 68 (2003) 177-191. 

Nuclear receptors (steroid receptors) that, when bound to their specific ligand (such as the hormone estrogen), alter the rate at which specific genes are transcribed and translated into cellular proteins. Because steroid hormones function through mechanisms intimately related to the regulation of gene expression, we consider them here only briefly (Section 12.8) and defer a detailed discussion of their action until Chapter 28. 

Mammals have several classes of hormones, distinguishable by their chemical structures and their modes of action (Table 23-1). Peptide, amine, and eicosanoid hormones act from outside the target cell via surface receptors. Steroid, vitamin D, retinoid, and thyroid hormones enter the cell and act through nuclear receptors. Nitric oxide also enters the cell, but activates a cytosolic enzyme, guanylyl cyclase (see Fig. 12-10). 

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-... 

In addition to the actions mediated by intracellular receptors, steroid hormones also demonstrate certain rapid (occurring within seconds) actions, which appear to be mediated by membrane effects/receptors this is true for vertebrate [114] and invertebrate [115] steroids. One presumes that the SAR studies for ecdysteroids which have been performed to date are predominantly determined by interaction of ecdysteroids with nuclear receptors, but one should bear in mind that in certain assay systems the... 

Steroid Receptors. Steroid receptors such as estrogen, progesterone, and androgen receptors are overexpressed in breast, ovarian, and prostate cancers. Estrogen and progesterone receptors are present in about 65% of human breast cancers. The presence or absence of these receptors in cases of breast carcinoma assists the determination of the therapeutic strategy (hormonal or chemical) that is likely to be effective. The successful Tc complex must cross the membrane lipid bilayer of the cell, and thus, the size and lipophilicity of the complex must be balanced with receptorbinding affinity. 

The general mechanism of receptor-mediated action of steroid hormones is very similar for each of the five classes. Briefly, the steroid enters the cell and binds to an intraceUnar protein. The resnlting receptor-steroid complex is converted in a poorly nn-derstood step called activation to a form that binds to specific, biologically active DNA seqnences (called hormone response elements, or HREs) of the nnclear chromatin. These HRE-bonnd receptor-steroid complexes recrnit various cofactors and then interact with the transcription complex containing RNA polymerase 11 to modify the rates of transcription of a nearby DNA sequence coding for an expressed protein (Fig. 2). This alteration of transcription rate is typically fast (15-30 min) (14). 

Figure 2 General steps in steroid hormone action and their assays. The basic model depicts steroid (S) binding to its receptor molecule (R) to form receptor-steroid complexes (RS), which attach to biologically active DNA binding sites (HRE) to eventually produce changes in the levels of specific proteins. Experimental techniques to follow R at various stages in this pathway are indicated at the first point that each method can detect a signal. Most methods can also be used to detect receptors at any step downstream of the one for which it is first used.

Regardless of whether the initially formed receptor-steroid complex is cytoplasmic or nuclear, a still poorly understood process called activation (or transformation) converts the complex into a species with increased affinity for DNA and for nnclei. The term activation was defined before it was possible to examine receptor binding to the promoter regions of endogenons genes. This definition may need revision becanse it is now clear... 

Simons SS Jr. Factors influencing association of glucocorticoid 95. receptor-steroid complexes with nuclei, chromatin, and DNA interpretation of binding data. In Glucocorticoid Hormone Action. 

Takeshita A, Koibuchi N, Oka J, et al. Bisphenol-A, an environmental estrogen, activates the human orphan nuclear receptor, steroid and xenobiotic receptor-mediated transcription. Eur J Endocrinol 2001 145 513-17. 

The steroid molecule is hydrophobic and is able to diffuse through the cell membrane and finds its receptor waiting for it in the cytoplasm of the cell. Receptor and steroid combine and the complex travels across the nuclear membrane into the nucleus whereupon it binds (still as the receptor/steroid complex) to an acceptor site on the cell s DNA. This binding then switches on transcription and the synthesis of mRNA. 

Horwitz KB, Costlow ME, McGuire WL (1975) MCF-7 a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors. Steroids 26(6) 785-795... 

Nuclear receptors, steroid hormone receptors Mineralocorticoid receptor Aldosterone (agonist)... 

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