Hormones effector systems

The G-proteins are a family of guanine nucleotide (GTP or GDP) binding proteins that are a component of several hundred hormone-effector systems or hgand-binding... 

The action of a hormone is defined as the primary effect on a cell, usually the binding of the hormone to a specific receptor and the resultant interaction between the hormone-receptor complex and an effector system within the cell. The effect of a hormone is an experimental observation that is made either in vitro or in vivo it can be molecular, biochemical or physiological but, when a sufficient number of effects are established, a relationship between the action and effects can be drawn. This can best be described as a pyramid (Figure 12.2). The. function of a hormone is an... 

For a cell surface receptor, the binding of the hormone must change the activity of an effector system that results in a change in concentration of an intracellular messenger. This is achieved by location of the effector system on the cytosolic side of the membrane, although the receptor and effector system may be combined in one complex. 

Despite the existence of a large number of hormones, only four effector systems for linking hormone binding to an intracellular effect have been described ... 

The effector systems result in changes in messenger systems that then cause the effects of the hormone. Not surprisingly, the effects of the hormone depend on which hormone is being considered. To illustrate this four hormones - insulin, cortisol, adrenaline and glucagon - are discussed. 

Although pheromones can be considered as a special form of odorants (scents), their actions, effects and functions have similarities to those of hormones. They bind to a specific receptor which then activates an effector system, which initiates an action potential. They bind to specific sensory cells, the neurones, in the olfactory epithelium, which is located on the roof of the nasal cavities. The epithelium consists of three types of cells, basal, supporting and sensory cells (neurones). The neurones are bipolar, that is they possess a single dendrite, which extends from the cell body to the surface of the olfactory epithelium, and an axon that forms a synapse with a nerve that transfers information to the olfactory centre in the brain. The epithelium is covered with a thick layer of mucus, in which the pheromones dissolve. The mucus contains proteins that bind the pheromone(s) for delivery to the olfactory receptors and then to remove them once they have been detected. 

This, at one time, was described as spare receptors but this is a misinterpretation of the role of the relationship. The response of the effector system is most sensitive to the change in hormone concentration when it is below the value of the dissociation complex. This principle is the same as that for the binding of a regulatory molecule to an enzyme (Chapter 3). 

These principles are similar to those that govern the relationship between an enzyme and its catalytic activity. For the hormone, R is equivalent to the enzyme, H to the substrate, and hormone-receptor complex to the enzyme-substrate complex. The activity of the substrate effector system is similar to the transition state. The cellnlar response to the hormone is similar to the catalytic role of the enzyme in the cell (Chapter 3),... 

Figure 12.16 Multiple sites of hormone effects on the same biochemical process. The hormone binds to its receptor activating the effector system which increases the activity of two separate reactions in the same biochemical pathway (process) to increase flux through the pathway. This means that the flux can change without large changes in the concentrations of intermediates in the pathway, i.e. activation of E and E4 ensures increased flux from S to the product P with little change in the concentrab ons of A, B or C.

Slow (adaptative) changes in Na+/H+ exchange activity have been observed in response to several hormonal effectors under pathological situations (Sacktor and Kinsella, 1988). These actions are mediated by changes either in the kinetic properties of the system or in the number of functional exchangers. 

However, chronic administration (e.g. as a depot injection) evokes an initial agonist phase of several days to weeks, followed by a suppression of gonadotrophin secretion. The precise molecular site of action of this process is unclear, but it is thought to involve an initial loss of receptors, followed by an uncoupling of receptors from their effector systems. Chronic administration is used clinically in the treatment of sex-hormone responsive tumors such as prostate and breast cancer. 

In addition to factors, hormones, and neurotransmitters, known to act through receptors that couple to G proteins, Table I also lists effector systems that are or may be affected directly by activated G. Of these effector systems, positive and negative regulation of adenylyl cyclase, activation of phospholipases, activation of cGMP-PDE in photoreceptor cells, and activation of K+ channels are well docu-... 

Many hormones, which bind to cell surface receptors, stimulate their effector systems to generate an intracellular second message by interacting with specific guanine nucleotide regulatory proteins (G-proteins) [85-89]. 

Peptide hormones bind to cell-surface receptors and the conformational change resulting from this binding activates an effector system, which is in turn responsible for the downstream actions of the hormone (Figure 28-1). For most peptide hormones, the intracellular effector that is activated... 

These are receptors for many hormones and neurotransmitters and are coupled to effector systems by a G-protein. 

These concepts of information transduction by membranes may be used to integrate the scattered observations on the biological effects of interactions of 3,6-3-glticans with plant cells. The observation that chemically different groups of compounds may elicit the production of the same response such as wilting or formation of a phytoalexin, may be explained in terms of multiple receptors coupled to a single effector system which initiates the intracellular response. This would be analogous to the adenyl cyclase of the adipocyte which is stimulated by seven different hormones and inhibited by at least three others (124). In the... 

A1 adenosine receptors are inhibitory in the central nervous system. A receptors were originally characterized on the basis of their ability to inhibit adenylyl cyclase in adipose tissue. A number of other G-protein-mediated effectors of A receptors have subsequently been discovered these include activation of K+ channels, extensively characterized in striatal neurons [13], and inhibition of Ca2+ channels, extensively characterized in dorsal root ganglion cells [14]. Activation of A receptors has been shown to produce a species-dependent stimulation or inhibition of the phosphatidylinositol pathway in cerebral cortex. In other tissues, activation of A receptors results in synergistic activation of the phosphatidylinositol pathway in concert with Ca2+-mobilizing hormones or neurotransmitters [15]. The effectors of A adenosine receptors and other purinergic receptor subtypes are summarized in Table 17-2. 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

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