Hormone protein complex

A dynamic equilibrium exists between the bound and the free fractions hormone-protein complex protein + free hormone... 

While many hormones bind to surface receptors the steroid hormones, which are lipid in nature, pass through the cell membrane and bind to receptor proteins in the nucleus. The resulting hormone-protein complexes induce changes in gene expression through regulation of transcription (Fig. 11-1, top). These receptors are considered in Chapter 22 and hormones are considered further in Chapter 30. 

With the availability of labeled hormones of high specific activity and the application of the principles of affinity chromatography, researchers were able to isolate cellular proteins that bind to plant hormones in vitro. Such proteins have been referred to as receptor proteins, binding proteins, or acceptor proteins. Tacit in the concept of hormone receptor proteins is the stereo-specific interaction of the hormone and the receptor protein (19). The resulting hormone-protein complex participates in growth processes that depend on new or enhanced protein synthesis. Advances in molecular biology and related sciences have enabled many researchers to study the role of receptors in the control of nuclear functions or other activities and to determine the site of primary hormonal action. 

In humans, the hypothalamic-derived protein and the hormone noncovalent complexes are packaged in neurosecretory granules, then migrate along axons at a rate of 1 4 mm/h until they reach the posterior pituitary where they are stored prior to release into the bloodstream by exocytosis (67). Considerable evidence suggests that posterior pituitary hormones function as neurotransmitters (68) vasopressin acts on the anterior pituitary to release adrenocorticotropic hormone [9002-60-2] (ACTH) (69) as well as on traditional target tissues such as kidneys. Both hormones promote other important central nervous system (CNS) effects (9,70). 

FIGURE 15.21 Hormone (H) binding to its receptor (R) creates a hormone receptor complex (H R) that catalyzes GDP-GTP exchange on the o -subunit of the heterotrimer G protein (G ), replacing GDP with GTP. The G -subunit with GTP bound dissociates from the /37-subunits and binds to adenylyl cyclase (AC). AC becomes active upon association with G GTP and catalyzes the formation of cAMP from ATP. With time, the intrinsic GTPase activity of the G -subunit hydrolyzes the bound GTP, forming GDP this leads to dissociation of G GDP from AC, reassociation of G with the /Sy subunits, and cessation of AC activity. AC and the hormone receptor H are integral plasma membrane proteins G and G are membrane-anchored proteins. 

Thus far, the discussion of G-proteins and effector enzymes has assumed that a ligand has engaged with its surface receptor. There is however, an important example of an alternative mechanism to activate an effector without the direct involvement of G-protein complex. NO is a local hormone, a neurotransmitter and part of the cell s armoury of oxidizing agents called free radicals. 

Second messengers often involved Protein kinases activated Hormone-receptor complex binds hormone response elements (HRE, of enhancer regions) inDNA... 

Raymond, J. R. (1994) Hereditary and acquired defects in signaling through the hormone-receptor-G protein complex. Am. J. Physiol. 266, 163-174. 

The hormone-receptor complex directly increases the activity of an enzyme, usually a protein kinase (Figure 12.4) or a phospholipase (Figure 12.5). 

Figure 12.8 Effector mechanism activation of a specific gene by hormone-receptor complex binding to DNA. A steroid is used to illustrate the mechanism. The hormone enters the cell and binds to its receptor (R) in the cytosol, the hormone-receptor complex enters the nucleus and binds to a specific sequence in the DNA that stimulates transcription of a gene or genes the resultant increase in mRNA increases the synthesis of specific proteins. The binding site on the DNA is specific and is usually termed a response element. Thyroxine (i.e. triiodothyronine) also uses this effector mechanism. Activation of genes, RNA processing to produce mRNA and translation are described in Chapter 20 (see Figures 20.20, 20.21 and 20.22).

Figure 12.20 The G-protein activation/inactivation cycle. When the G-protein is associated with GTP, it is active when it is associated with GDP it is inactive. The hormone-receptor complex is the GTP exchange factor, which exchanges GDP for GTP to convert the inactive form to the active form. A GTPase activity inactivates the G-protein by hydrolysing GTP.

Figure 12.21 Effect of the hormone-receptor complex on activation of the G-protein and the resultant effect on the activation of adenyl cyclase. The hormone bind to the receptor to produce the hormone-receptor complex that activates to G-protein.

The mechanism by which Na" is reabsorbed in coupled exchange with and K+ in the collecting duct has been discussed previously that is, Na+-driven K+ secretion is partially under mineralocorticoid control. Aldosterone and other compounds with mineralocorticoid activity bind to a specific mineralocorticoid receptor in the cytoplasm of late distal tubule cells and of principal cells of the collecting ducts. This hormone-receptor complex is transported to the cell nucleus, where it induces synthesis of multiple proteins that are collectively called aldosterone-induced proteins. The precise mechanisms by which these proteins enhance Na+ transport are incompletely understood. However, the net effect is to increase Na" entry across apical cell membranes and to increase basolateral membrane Na+-K+-ATPase activity and synthesis. 

Upon entering the cell, the steroid molecule initially binds to the steroid receptor protein (E domain) to form the steroid-hormone-receptor complex. This complex concomitantly binds to an additional eight or more other peptides (also via the E domain) these peptides are termed chaperone peptides and consist of macromolecules such as heat shock proteins (e.g., hsp70, hsp90). The chaperone peptides help to twist and turn the steroid receptor protein into an improved three-dimensional shape for final and optimal binding of the steroid molecule. Following binding of the chaperone peptides, the steroid-hormone-receptor complex becomes a mature steroid-hormone-receptor... 

An initial amplification often occurs at the level of the hormone-receptor complex. An activated receptor is capable of activating many downstream effector proteins. 

The signal transmission by the hormone-receptor complex can be actively inhibited via covalent modifications (e.g. protein phosphorylation) which deactivate the hormone-receptor complex. Another mechanism for termination of signaling pathways is the... 

---