Second messenger systems, hormone action

See also Second Messenger Systems, Hormone Receptors, Oncogenes and Cell Signalling, Diabetes, Action of Insulin... 

Hormonal actions on target neurons are classified in terms of cellular mechanisms of action. Hormones act either via cell-surface or intracellular receptors. Peptide hormones and amino-acid derivatives, such as epinephrine, act on cell-surface receptors that do such things as open ion-channels, cause rapid electrical responses and facilitate exocytosis of hormones or neurotransmitters. Alternatively, they activate second-messenger systems at the cell membrane, such as those involving cAMP, Ca2+/ calmodulin or phosphoinositides (see Chs 20 and 24), which leads to phosphorylation of proteins inside various parts of the target cell (Fig. 52-2A). Steroid hormones and thyroid hormone, on the other hand, act on intracellular receptors in cell nuclei to regulate gene expression and protein synthesis (Fig. 52-2B). Steroid hormones can also affect cell-surface events via receptors at or near the cell surface. 

FIGURE 52-2 There are two modes of hormonal action. (A) Activation of cell-surface receptors and coupled second-messenger systems, with a variety of intracellular consequences. (B) Entry of hormone into the target cell, binding to and activation of an intracellular receptor and binding of the receptor-hormone complex to specific DNA sequences to activate or repress gene expression. DAG, diacylglycerol HRE, hormone-response element. 

The effects of Li+ upon this system have been reviewed in depth by Mork [131]. Animal studies originally demonstrated that Li+ inhibits cAMP formation catalyzed by adenylate cyclase in a dose-dependent manner [132]. The level of cAMP in the urine of manic-depressive patients changes with mental state, being abnormally elevated during the switch period between depression and mania it is proposed that Li+ s inhibitory effect upon adenylate cyclase activity may correct this abnormality. Subsequent research, in accord with the initial experiments, have shown that Li+ s interference with this second messenger system involves more than one inhibitory action. At therapeutic levels, Li+ inhibits cAMP accumulation induced by many neurotransmitters and hormones, both in... 

In no model pheromone biosynthetic system is the molecular mechanism of hormonal regulation completely understood. The mechanism of action of JH and the nature of its receptor remain one of the mysteries of insect science, and the clear-cut action of JH by itself in inducing specific genes in pheromone production in bark beetles offers an excellent model for study. A better understanding of the PBAN receptor and the second messenger system it triggers as well as the steps regulated in pheromone biosynthesis is also needed. The next several years should see some of the key questions answered in model insects. 

Most hormones influence cell metabolism through second messengers, as already stated. There are two major forms the cyclic AMP (see Chapter 10) and the Ca2+ systems. The various hormones, neurotransmitters, and other metabolic mediators elicit the activation of either one or the other system by binding to their specific receptors. Table 16.6 summarizes the second messenger systems used by the various hormones. The details of the mode of action of each second messenger system are discussed here. 

In the past few years our understanding of a new second messenger system involving inositol phospholipids has developed rapidly. It is clear the action of many hormones and neurotransmitters depends on the hydrolysis of membrane phosphoin-ositides. Agonists induce the cleavage of Ptdlns 4,5-P2, resulting in the formation... 

Norepinephrine (NE) and epinephrine (EPI) act as neurotransmitters and hormones in both the peripheral and central nervous systems (CNS). NE is released from neurons throughout the CNS and periphery to participate in a variety of physiological fimctions, while both NE and EPI are released from the adrenal medulla in response to stress. NE and EPI modulate fluid homeostasis, cardiac fimction, energy metabolism, and may play a role in depression. At the cellular level, these actions are mediated by multiple adrenergic receptor (AR) subtypes and second messenger systems. 

Lithium is one of the group lA alkali metals (like potassium and sodium) and is not normally present in the body. It acts predominantly through the phosphatidylinositol (PI) second messenger system, causing alterations in calcium- and protein kinase C (PKC)-mediated processes. Lithium can also alter the adenylate cyclase (AC) system, but this action is probably related to its toxic effects. Many calcium-dependent systems may be affected by lithium, among them regulation of receptor sensitivity, parathyroid hormone release, and proper functioning of intracellular microtubule structures. - ... 

Many hormones, such as the hormonal amines and all pep-tidic hormones, are unable to penetrate the lipid matrix of the cell membrane, and thus depend on the presence of receptor sites at the surface of target cells. As listed in Table 30-4, there are several types of cell membrane receptors for these hormones, each of which is coupled to a distinct set of intracellular postreceptor pathways. The surface receptors all initiate postreceptor events that involve the phosphorylation of one or more intracellular proteins, some of which are enzymes whose activities depend on the state of phosphorylation. In two of these cases, an intracellular second messenger is utilized to implement the hormonal action and involves G-protein-coupled receptors. One is coupled to the adenylate cyclase-cAMP system and the other is associated with the phosphatidylinositol-Ca + pathway (IP3 pathway). 

C10H12N5O6P 329.208 Found in several higher plants, bacteria and most animal cells. Excreted in human urine. Formed by action of adenate cyclase on ATP in vivo. Intracellular regulator of several cellular processes. Involved in hormone-mediated biological systems as a second messenger . Cryst. + IH2O. Sol. H2O. 

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