Autocrine

Transport in the blood is no longer a requisite for a hormonal response. Responses can occur after release of hormones into the interstitial fluid with binding to receptors in nearby ceUs, called paracrine control, or binding to receptors on the ceU that released the hormone, called autocrine control. A class of hormones shown to be synthesized by the tissue in which they act or to act in the local ceUular environment are the prostaglandins (qv). These ubiquitous compounds are derived from arachidonic acid [506-32-1] which is stored in the ceU membranes as part of phosphoHpids. Prostaglandins bind to specific ceUular receptors and act as important modulators of ceU activity in many tissues. 

P and Pg, exist in foUicular fluid. Control of inhibin secretion involves a feedback relationship in which circulating FSH stimulates inhibin secretion, which in turn reduces the secretion of FSH (8). Both the homo- and the heterodimers of the P-subunits of inhibin promote the secretion of FSH and thus have been termed activins. Activin is secreted by the ovary and the testes into the circulation. In addition, both inhibin and activin have intragonadal autocrine and paracrine effects that influence gonadal steroidogenesis (9). 

Protection appears to be mediated by PKC activation. Radiation induces b-EGE production by these cells, allowing a survival-associated positive autocrine loop to develop. 

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

Besides direct apoptosis effectors, there are a number of other diugs which influence the above explained apoptosis pathways more indirectly. This class of diugs includes molecules which inhibit survival pathways like e.g. the Ras/Raf kinase pathway, the NF-kB pathway and many others. Also inhibitors of survival cytokines which are sometimes produced by cancer cells in an autocrine fashion can render cells susceptible to apoptosis and, hence, effective cancer therapy. These include, but are not limited to, ligands for dependence receptors and cytokines like e.g. interleukin-4. 

Contraction of guinea pig parenchyma ( ) Autocrine activation of PLA2 (guinea pig)... 

PGs act locally in an autocrine or paracrine fashion in the tissues in which they are synthesized, rather than as circulating hormones, which act at a distant site. For this reason, studies localizing the enzymatic machinery, which synthesize prostaglandins, are informative with respect to the site of PG actions. PG synthesis is... 

Somatostatin acts on various organs, tissues and cells as neurotransmitter, paracrine/autocrine and endocrine regulator on cell secretion, smooth muscle contractility, nutrient absorption, cell growth and neurotransmission [1]. Some of its mainly inhibitory effects are listed in Table 1. Somatostatin mediates its function via a family of heptahelical G-protein-coupled receptors termed... 

It is of interest that proteins termed motility factors (55-70 kD) are secreted by fetal cells and some tumor cells. These proteins act as autocrine factors and stimulate rapid movement by these cells. Motility factors induce the formation of cell processes that are packed with actin filaments and have an increased number of receptors for the matrix proteins laminin and fibronectin. The latter enhance the ability of the cells to bind to the extracellular matrix. Thus, it is likely that motility factors influence the organization of the cytoskeleton through changes taking place at the cell surface (reviewed by Warn and Dowrick, 1989). 

The secretion of extracellular matrix proteins is also a function of smooth muscle cells but, since it occurs concurrently with other activities, it does not seem to constitute a physiological state. However, the fraction of the cellular resources which are devoted to it must be regulated these regulatory mechanisms are virtually unknown. In addition, it should be anticipated that autocrine activity occurs as well, involving peptides, prostaglandins, cytokines, and nitric oxide. 

Figure 1. Autocrine and paracrine factors. Many animal cells secrete regulatory factors called autocrine factors, which then interact with specific receptors on the surface of the same cells, so as to modulate cell function. Animal cells may also secrete regulatory factors called paracrine factors, which interact with specific receptors on different cells in the same locale, modulating their functional properties.

TGFs are secreted by animal cells following their biosynthesis. Subsequently, these TGFs may either stimulate the growth of the very cells that have produced them (in this case, the TGFs act as autocrine factors), or may stimulate the growth of other adjacent cell types (in this case, the TGFs act as paracrine factors). 

Fig. 4.4 Simplified hypothesis of the mechanism of gpI20-induced dorsal root gangUon (DRG) neurotoxicity. CXCR4 binding on Schwann cells by SDF-Ia or gpI20 results in the release of RANTES, which induces tumor necrosis factor (TNF)-a production by DRG neurons, and subsequent TNFRl-mediated neurotoxicity in an autocrine/paracrine fashion. Reproduced with permission of John Wiley Sons, Inc. (Keswani et al. 2003b)...

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