Hormones local

Animal cells can modify arachidonic acid and other polyunsaturated fatty acids, in processes often involving cyclization and oxygenation, to produce so-called local hormones that (1) exert their effects at very low concentrations and (2) usually act near their sites of synthesis. These substances include the prostaglandins (PG) (Figure 25.27) as well as thromboxanes (Tx), leukotrienes, and other hydroxyeicosanoic acids. Thromboxanes, discovered in blood platelets (thrombocytes), are cyclic ethers (TxBg is actually a hemiacetal see Figure 25.27) with a hydroxyl group at C-15. 

The biosynthesis of eicosanoids utilizes several enzymes till the ultimate bioactive ligand is obtained. The literature is very rich in PAL studies on these enzymes and the local hormone receptors therefore only some major results on the key biotransformations and receptors are represented here. 

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. 

Three dietary intervention studies reported the effects of soy or soy phytoestrogen consumption on reproductive hormones in men and very modest alterations of doubtful clinical significance were found (Habito et al., 2000 Nagata et al., 2001). None of these studies evaluated the prostate itself, and it is possible that soy consumption alters local hormone metabolism and action within the gland. 

Figure 11.30 Mechanisms of regulation of phospholipase A2. In all these processes described above, it is phospholipase A that carries out the hydrolysis of membrane phospholipid. Cytokines are local hormones produced by immune cells, T-lymphocytes and macrophages (Chapter 17). Other factors relate to shear stress in endothelial cells and those that stimulate release of granules from mast cells. Eicosanoids are present in the granules and they must be re-synthesised after degranulation in the mast cells. Here the enzymes described above must be present in mast cells.

The gap across the synapse is so small that the chemical messenger (neurotransmitter) crosses the cleft in less than a millisecond. Within the brain there are more than 50 neurotransmitters, which include amino acids, amines, purines, peptides and some gases. In contrast, in the peripheral nervous system there are only two, acetylcholine and noradrenaline. One of several questions concerning the concept of neurotransmitters is whether they differ, in principle, from local hormones (See below and Chapter 12). 

Type III neurotransmitters These are peptides (neuropeptides), and most are considered to be neuromodulators rather than neurotransmitters. As a further complication, some of these are also found in the intestine, where they act as local hormones or even endocrine hormones (Chapter 4 Table 14.1). 

To respond to follicle-stimulating hormone (FSH) and testosterone, which stimulate the production of local hormones that increase maturation of the sperm. 

Different chemicals provide communication between tissues/organs of the reproductive system. They are classified into three groups steroids, peptides and fatty messengers. They can also be classified as endocrine or local hormones, some of which are discussed in Chapter 12. 

Normal endothelial cells produce nitric oxide, which relaxes smooth muscle, whereas damaged cells release less nitric oxide but more of a local hormone, endothelin, which stimulates contraction of smooth muscle (Figure 22.4). 

A large number of local hormones are derived from polyunsaturated C18-C22 fatty acids. These... 

Serotonin is an important neurotransmitter, a local hormone in the gut, a component of the platelet clotting process, and is thought to play a role in migraine headache. Serotonin is also one of the mediators of the signs and symptoms of carcinoid syndrome, an unusual manifestation of carcinoid tumor, a neoplasm of enterochromaffin cells. In patients whose tumor is not operable, a serotonin antagonist may constitute a useful treatment. 

Substance P is present in the central nervous system, where it is a neurotransmitter (see Chapter 21), and in the gastrointestinal tract, where it may play a role as a transmitter in the enteric nervous system and as a local hormone (see Chapter 6). 

Like many other neuropeptides, NT serves a dual function as a neurotransmitter or neuromodulator in the central nervous system and as a local hormone in the periphery. When administered centrally, NT exerts potent effects including hypothermia, antinociception, and modulation of dopamine neurotransmission. When administered into the peripheral circulation, it causes vasodilation, hypotension, increased vascular permeability, increased secretion of several anterior pituitary hormones, hyperglycemia, inhibition of gastric acid and pepsin secretion, and inhibition of gastric motility. It also exerts effects on the immune system. 

Lipid peroxidation has often been regarded simply as an undesirable side reaction, but it is also a normal part of metabolism. Initiated by enzymatically generated radicals, peroxidation occurs as specific metabolic pathways, such as the arachidonate cascade, which leads to a variety of local hormones and other substances (Eq. 21-16).254 2563... 

AMP can be converted by the action of AMP 5-nucleotidase to adenosine (step c, Fig. 25-17), which is thought to be an important local hormone or second... 

Outline of pathways for the biosynthesis of major cellular lipids (other than cholesterol) in a mammalian cell. Most of the metabolism of these lipids occurs on membrane surfaces because of the insoluble nature of the substrates and products. These lipids play three major roles (l) they act as a storehouse of chemical energy, as with triacylglycerols (2) they are structural components of membranes (boxed compounds) and (3) they act as regulatory compounds (underlined), either as eicosanoids, which act as local hormones, or as phosphorylated inositols and diacylglycerols, which function as second messengers. 

How does aspirin differ from morphine Aspirin has three main beneficial effects in your body. It blocks pain in the mild-to-moderate range, and it reduces both inflammation and fever. Its effects on pain derive from its actions not on neuropeptides, such as the endogenous opiates in the brain, but on a local hormone called prostaglandin that is released at the site of bodily pain. When a cell in your body is damaged or injured, prota-glandins are rapidly synthesized and released from the injured cells. Prostaglandins help mediate pain in the injured areas. They sensitize your pain-sensing neurons to mechanical stimulation,... 

All agonists in this therapeutic group decrease the sensation of painful stimuli, which is their main clinical application. They tend to subdue dull, persistent pain rather than sharp pain, but this difference is to some extent dose dependent. The major difference between the non-opioid analgesics such as aspirin and the opiates is that the former reduce the perception of peripherally mediated pain, by reducing the synthesis of local hormones that activate the pain fibres, whereas the latter attenuate the affective reaction to pain without affecting the perception of pain. This clearly suggests that the site of action of the opiate analgesics is in the central nervous system. 

---