Hormonal signalling

Hormones Signal the Release of Fatty Acids from Adipose Tissue... 

Hormonal Signals Regulate ACC and Fatty Acid Biosynthesis... 

FIGURE 25.17 Hormonal signals regulate fatty acid synthesis, primarily through actions on acetyl-CoA carboxylase. Availability of fatty acids also depends upon hormonal activation of triacylglycerol lipase. 

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

Growth factor and hormone signalling cascades link mTORCl dysregulation to cancer and Hamartoma syndromes. 

Figure 18-6. Control of phosphorylase in muscle. The sequence of reactions arranged as a cascade allows amplification of the hormonal signal at each step, (n = number of glucose residues G6P, glucose 6-phosphate.)...

The adenohypophysis does not have a direct anatomical connection with the hypothalamus therefore, regulation of hormone secretion by way of neuronal signals is not possible. Instead, these two structures are associated by a specialized circulatory system and the secretion of hormones from the adenohypophysis is regulated by hormonal signals from the hypothalamus (see Figure 10.2). Systemic arterial blood is directed first to the hypothalamus. The exchange of materials between the blood and the interstitial fluid of the hypothalamus takes place at the primary capillary plexus. The blood then flows to the adenohypophysis through the hypothalamic-hypophyseal portal veins. Portal veins are blood vessels that connect two capillary beds. The second capillary bed in this system is the secondary capillary plexus located in the adenohypophysis. 

Reduction of N()2 to NO Reduction of N20 to N2 Copper storage Transcription factor Hydroxylation of Dopa Production of Protoporphyrin IX Hormone signalling Oxidation to methanol Production of signal peptides Copper pump Copper transfer... 

Hormone signals are turned off by degrading or excreting them so that the signal disappears. The same thing happens with neurotransmitters. 

The primary hormonal signals serve as extracellular signals that are interpreted by a signal transduction apparatus and turned into signals within the cell—these second messengers such as cAMP and fructose 2,6-bisphosphate warn individual enzymes within the cell about what s happening outside. 

Calcitonin lowers serum Ca2+ and Pi levels, primarily by inhibiting the process of bone resorption, but also by decreasing resorption of Pi and Ca2+ in the kidney. Calcitonin receptors are predictably found primarily on bone cells (osteoclasts) and renal cells, and generation of cAMP via adenylate cyclase activation plays a prominent role in hormone signal transduction. 

Piwien-Pilipuk, G., Huo, J.S., and Schwartz, J. 2002. Growth hormone signal transduction. Journal of Pediatric Endocrinology and Metabolism 15(6), 771-786. 

Ligand-bound corticosteroid receptors have been shown to interact to form heterodimers with other transcription factors, such as the jun protein. Such interactions are responsible for transactivation of the ds-regulatory sites known as AP-1 sites and for the glucocorticoid-mediated suppression of transcription, such as that seen in the pro-opiomelanocortin gene. A number of such specific protein interactions have been reported these interactions and their locations relative to other transcription factors transform a ubiquitous steroid hormone signal into a tissue-specific, graded cellular response. 

Kliewer, S.A., Lehmann, J.M., Milburn, M.V. and Willson, T.M. (1999) The PPARs and PXRs nuclear xenobiotic receptors that define novel hormone signaling pathways. Recent Progress in Hormone Research, 54, 345-367. 

EIN2 operating downstream of CTRl is considered a central component in the ethylene signaling pathway and also it is assumed to be a common node mediating crosstalk of multiple hormone signal transduction pathways. " ... 

Flatt T, Moroz LL, Tatar M, Heyland A (2006) Comparing thyroid and insect hormone signalling. Integr Comp Biol 46 777-794... 

Depending on the type of hormone, hormone signals are transmitted to the target cells in different ways. Apolar (lipophilic) hormones penetrate the cell and act in the cell nucleus, while polar (hydrophilic) hormones act on the external cell membrane. 

Each hormone is the center of a hormonal regulation system. Specialized glandular cells synthesize the hormone from precursors, store it in many cases, and release it into the bloodstream when needed (biosynthesis). For transport, the poorly water-soluble lipophilic hormones are bound to plasma proteins known as hormone carriers. To stop the effects of the hormone again, it is inactivated by enzymatic reactions, most of which take place in the liver (metabolism). Finally, the hormone and its metabolites are expelled via the excretory system, usually in the kidney (excretion). All of these processes affect the concentration of the hormone and thus contribute to regulation of the hormonal signal. 

The hydrophilic hormones are derived from amino acids, or are peptides and proteins composed of amino acids. Hormones with endocrine effects are synthesized in glandular cells and stored there in vesicles until they are released. As they are easily soluble, they do not need carrier proteins for transport in the blood. They bind on the plasma membrane of the target cells to receptors that pass the hormonal signal on (signal transduction see p.384). Several hormones in this group have paracrine effects—i.e., they only act in the immediate vicinity of their site of synthesis (see p. 372). 

Nuclear receptors exert their different transcriptional functions through interactions with and the recruitment of co-factors to responsive promoters. Co-factors are either positive or negative regulatory proteins and are classified as co-activators, which promote, or co-repressors, which attenuate the activity of nuclear hormone receptors [46]. The molecular mechanisms that regulate the mutually exclusive interactions of the nuclear receptor with either class of co-factors have been analysed by crystallographic studies. Functional and structural studies have shown that co-activators interact with the transactivation function (AF) of nuclear hormone receptors via short, leucine-rich motifs (LXXLL) termed NR boxes , thereby transducing hormonal signals to the basal transcription machinery [47]. 

---