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Thyroid cascade

V. Step-by-step analysis of the thyroid cascade and the effects of potential ecotoxicants... [Pg.397]

Although this literature has been reviewed extensively16,36,47 54-56 65 it is still not understood precisely how the fish thyroid system responds to any given xenobiotic and what the biological consequences might be. In light of this we have focused on possible mechanisms of fish thyroid disruption. We have commenced with brief overviews of the properties of thyroid hormones (TH) and the thyroid cascade and have then considered the problems inherent in evaluating fish thyroidal responses. [Pg.397]

However, we have devoted most of the review to a step-by-step analysis of the thyroid cascade , focusing on laboratory studies of chemicals likely to have direct effects at a given step. [Pg.398]

Fig. 2. The thyroid cascade showing the sites for central control and for systemic and local peripheral control. Also shown is the possibility of an exogenous TH supply from food. Fig. 2. The thyroid cascade showing the sites for central control and for systemic and local peripheral control. Also shown is the possibility of an exogenous TH supply from food.
The final point is perhaps the most critical as well as the most overlooked. Even under normal circumstances the fish thyroid cascade responds to a wide array of environmental variables and changes in whole-animal physiologic state. In fact, much fish thyroid literature (unrelated to ecotoxicants) documents thyroidal responses to variables such as temperature, stressors, nutritional availability and sexual state. The thyroidal system is also pivotal in the total endocrine network. Consequently,... [Pg.401]

Figure 25-8. Control of adipose tissue lipolysis. (TSH, thyroid-stimulating hormone FFA, free fatty acids.) Note the cascade sequence of reactions affording amplification at each step. The lipolytic stimulus is "switched off" by removal of the stimulating hormone the action of lipase phosphatase the inhibition of the lipase and adenylyl cyclase by high concentrations of FFA the inhibition of adenylyl cyclase by adenosine and the removal of cAMP by the action of phosphodiesterase. ACTFI,TSFI, and glucagon may not activate adenylyl cyclase in vivo, since the concentration of each hormone required in vitro is much higher than is found in the circulation. Positive ( ) and negative ( ) regulatory effects are represented by broken lines and substrate flow by solid lines. Figure 25-8. Control of adipose tissue lipolysis. (TSH, thyroid-stimulating hormone FFA, free fatty acids.) Note the cascade sequence of reactions affording amplification at each step. The lipolytic stimulus is "switched off" by removal of the stimulating hormone the action of lipase phosphatase the inhibition of the lipase and adenylyl cyclase by high concentrations of FFA the inhibition of adenylyl cyclase by adenosine and the removal of cAMP by the action of phosphodiesterase. ACTFI,TSFI, and glucagon may not activate adenylyl cyclase in vivo, since the concentration of each hormone required in vitro is much higher than is found in the circulation. Positive ( ) and negative ( ) regulatory effects are represented by broken lines and substrate flow by solid lines.
Toxicologically the function of the terminal hormones of endocrine cascades (i.e., steroid, retinoid, thyroid hormones) appear to be most susceptible to disruption by chemicals. This is because many foreign molecules share sufficient characteristics with these hormone molecules to allow binding to the nuclear receptors of these hormones in either an agonistic or antagonistic fashion. The binding of the xenobiotic to the... [Pg.302]

A recently identified thyroid hormone cell surface receptor on the extracellular domain of integrin alphaVbeta (3) leads to the activation of the mitogen-activated protein kinase (MAPK) signal transduction cascade in human cell lines, Examples of MAPK-dependent thyroid hormone actions are plasma membrane ion pump stimulation and specific nuclear events, These events include serine phosphorylation of the nuclear thyroid hormone receptor, leading to co-activator protein recruitment and complex tissue responses, such as thyroid hormone-induced angiogenesis, The existence of this cell surface receptor means that the activity of the administered hormone could be limited through structural modification of the molecule to reproduce only those hormone actions initiated at the cell surface (8,9). [Pg.396]

TSH (also called thyrotropin), which is secreted by the pituitary, plays a central role in the regulation of growth and function of the thyroid gland. TSH receptors are functionally coupled to G-proteins thus, the extracellular stimulus by TSH is transduced into intracellular signals mediated by a number of G-proteins. Activation of Gs-protein results in the stimulation of the adenylate cyclase-cAMP-protein phosphorylation cascade. Other G-proteins coupled to TSH-receptor activation include Gg-protein, which mediates the phospholipase C-phosphatidylinositol 4,5-bisphosphate-Ca + signaling pathway (see Chapter 30 for a detailed discussion). [Pg.772]

Cannabinoids have been shown to induce cell cycle arrest in breast carcinoma (De Petrocellis et al. 1998), prostate carcinoma (Melck et al. 2000) and thyroid epithelioma cells (Bifulco et al. 2001). In breast carcinoma cells this has been ascribed to the inhibition of adenylyl cyclase and the cAMP/protein kinase A (PKA) pathway (Table 1). PKA phosphorylates and inhibits Raf-1, so cannabinoids prevent the inhibition of Raf-1 and induce prolonged activation of the Raf-l/MEK/ERK signalling cascade (Melck et al 1999). Cannabinoid-induced inhibition of thyroid epithelioma cell proliferation has been attributed to the induction of the cyclin-dependent kinase inhibitor p27 P (Portella et al. 2003). [Pg.631]

TSH binds a G protein-coupled receptor to activate adenylate cyclase and trigger a signaling cascade leading to thyroid hormone biosynthesis. [Pg.416]


See other pages where Thyroid cascade is mentioned: [Pg.397]    [Pg.399]    [Pg.399]    [Pg.401]    [Pg.402]    [Pg.402]    [Pg.405]    [Pg.408]    [Pg.409]    [Pg.397]    [Pg.399]    [Pg.399]    [Pg.401]    [Pg.402]    [Pg.402]    [Pg.405]    [Pg.408]    [Pg.409]    [Pg.158]    [Pg.158]    [Pg.269]    [Pg.368]    [Pg.895]    [Pg.111]    [Pg.402]    [Pg.276]    [Pg.516]    [Pg.171]    [Pg.112]    [Pg.114]    [Pg.315]    [Pg.111]    [Pg.62]    [Pg.92]    [Pg.48]    [Pg.799]    [Pg.158]    [Pg.158]    [Pg.177]    [Pg.2056]    [Pg.202]    [Pg.282]    [Pg.70]    [Pg.411]    [Pg.92]   
See also in sourсe #XX -- [ Pg.397 , Pg.409 ]




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