Autocrine secretion

Cantini, M., Massimino, M.L., Rapizzi, E., Rossini, K., Catani, C., Dalla Libera, L., Carraro, U. (1995). Human satellite cell proliferation in vitro is regulated by autocrine secretion of IL-6 stimulated by a soluble factor(s) released by activated monocytes. Biochem. Biophys. Res. Commun. 216 49-53. 

Kaplan D. Autocrine secretion and the physiological concentration of cytokines. Immuno Today 1996 17 303-4. 

The most recently discovered means of secretion is autocrine release (C3, H9, S8), by which cells stimulate their own growth. Trophic peptides bind to specific receptors in the membranes of their own cells (Fig. 4, last box). Autocrine secretion is supposed to play a decisive role in tumor and cancer development. The first... 

Malignant cells are said to produce growth faetors by a process called autocrine secretion, and several peptides have bear found to be involved (Hoffman, 1999, p. 64). It is noted that tyrosine kinase favors autoetine aetivity, but it is also noted that (unspecified) inhibitors do exist. 

Weintraub AS, Giachelli CM, Krauss RS, Almeida M, Taubman MB (1996) Autocrine secretion of osteopontin by vascular smooth muscle cells regulates their adhesion to collagen gels. Am J Pathol 149 259-272... 

Proliferation and migration of vascular smooth muscle cells (VSMC) is one of the hallmarks of atherosclerosis. Red wine polyphenols hinder the proliferation and migration of cultured SMCs stimulated by growth factors through inhibition of PI3K activity and p38 (MAPK) phosphorylation.In support, resveratrol reversibly arrests VSMC proliferation in early S phase of the cycle. Recent studies on SMCs demonstrate the anti-atherogenic actions of resveratrol via its ability to inhibit the autocrine secretion and the mitogenic effects of endothelin-... 

As noted previously, the evidence for the contribution of microtubules to amoeboid cell motility and chemotaxis is mixed [242]. The microtubule organizing center has been reported to be localized to either the front or rear side of the nucleus, depending upon the cell type [167, 187, 188]. Alterations in microtubules can affect fibroblast lamellipod extension and motility [150], but in some assays, chemotactic responses may be unaffected [202]. Alterations in acetylation enhance chemotactic ability [98]. Microtubules have been proposed to alter the stability of adhesion sites, enhancing their disassembly [II9]. In sum, microtubules are likely to be permissive for amoeboid motility and chemotaxis, and respond to polarization of the cell generated by the actin system with polarization of the microtubule system. This may in turn stabilize cell polarity and enhance overall chemotactic efficiency. In the absence of a strong external stimulus, or in cases in which autocrine secretion influences cell polarization, the microtubule apparatus may provide critical signals for cell polarity [164]. 

Perrone, C. E., D. Fenwick-Smith, and H. H. Vandenburgh. 1995. Collagen and stretch modulate autocrine secretion of insulin-like growth factor-1 and insulin-Uke growth factor binding proteins from differentiated skeletal muscle cells. / Biol Chem 270(5) 2099-106. 

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). 

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). 

IL-2 acts as a critical autocrine growth factor for T-cells, and the magnitude of the T-cell response is largely dependent upon the level of IL-2 produced. IL-2 also serves as a growth factor for activated B-lymphocytes. In addition to promoting proliferation of these cells, IL-2 (as well as some other interleukins) stimulates enhanced antibody production and secretion. In this way, it effectively potentates the humoral immune response. 

The factors are secreted into the extracellular milieu where they diffuse and then act in a paracrine fashion on other cells (Fig. 27-1). Indeed, there is evidence that this type of paracrine support is necessary to sustain neurons as they extend their processes over long distances in the developing nervous system [2]. An analogous process, autocrine stimulation, occurs when a cell synthesizes and secretes a growth factor to which the cell itself is responsive. In this case, the cell provides its own trophic support. 

The receptor for NGF is TrkA, a 140 kDa cell surface protein that specifically binds NGF, but not other neurotrophins [5, 6, 9]. TrkA is expressed on the neuronal cell body and on neuronal processes. In its action as a target-derived trophic factor, NGF is secreted within the target organ and it then binds to TrkA receptors present on the growing neuronal process or synapse. The NGF-TrkA complex is then internalized and subsequently translocated to the cell body by retrograde axonal transport. In those cells that respond to NGF through autocrine or paracrine mechanisms, the growth factor can bind to any of the widely distributed TrkA molecules on the neuronal membrane. 

Sabharwal, P. et al., Prolactin synthesized and secreted by human peripheral blood mononuclear cells An autocrine growth factor for lymphoproliferation, Proc. Nat. Acad. Sci., 89, 7713, 1992. 

Sabharwal, P, Varma, S., and Malarkey, W.B., Human thymocytes secrete luteinizing hormone An autocrine regulator of T-cell proliferation, Biochem. Biophys. Res. Com., 187, 1187, 1992. 

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