Oxytocin's story starts back in the early 1900s, when biochemists discovered that a substance from the posterior pituitary gland could promote labour contractions and lactation. When scientists later discovered the hormone responsible, they named it oxytocin after the Greek phrase meaning 'rapid birth'. Oxytocin is produced mainly by the brain's hypothalamus; in the 1970s, studies revealed that oxytocin-producing neurons send signals throughout the brain, suggesting that the hormone had a role in regulating behaviour.
Oxytocin production is controlled by a positive feedback mechanism. This mechanism allows the release of the oxytocin hormone when a trigger occurs. The hormone then causes an action in the body, such as the letdown of milk or the start of labor contractions, which signals more production of oxytocin. The feedback cycle continues until the action, such as childbirth or feeding the baby, is complete.
What we noticed was that all the rats that had received oxytocin straight into their brain immediately prior to being given alcohol, were up and moving about and seemed to be completely sober. Whereas all of the rats that had just been given the alcohol were, as we would predict from the dose that we were giving them, quite drunk. And so we thought, 'Wow, what's going on here?' It was almost as though the oxytocin was blocking the intoxicating effects of the alcohol.
Froemke's study1, published in April, showed that oxytocin temporarily suppresses inhibitory neurons — those that dampen neural activity — which allows excitatory cells to respond more strongly and reliably. “Our hypothesis is that the virgin brain is a blanket of inhibition, and that pairing the pup calls with oxytocin allows the network to be reconfigured,” says Froemke. The hormone may serve to amplify incoming signals and allow them to be recognized as behaviourally important. (It is at least possible, he says, that this same mechanism could explain why some human mothers feel they are uniquely tuned to a baby's cries.)
Tβ4 is the major monomeric actin-sequestering peptide in human tissues, and can bind globular actin (G-actin) in a 1:1 ratio and consequently involved in cytoskeletal regulation by inhibiting the polymerization of G-actin into fibrous actin (F-actin) [7]. In addition, Tβ4 is an ubiquitous naturally occurring molecule and is found at concentrations of 1 × 10−5 to 5.6 × 10−1 M in a variety of tissues and cell types, yet, no receptors for the protein have been identified [33]. A recent study suggests that internalization of exogenous Tβ4 is essential for its subsequent cellular functions [34]. Moreover, Tβ4 has been shown to be associated with, wound healing, hair growth, immunomodulation, and angiogenesis [7–9].
But this isn’t the only study to show the subtle side of oxytocin. Just three months ago, I wrote about research from Heejung Kim at the University of California, which showed how oxytocin’s effects vary across different cultures. To fulfil its many roles, oxytocin has to dock at a protein called the ‘oxytocin receptor’, encoded by a gene called OXTR.
The pore-forming subunit of the cardiac sodium channel Nav1.5 encoded by SCN5A is a critical determinant of myocardial excitability and conduction. Loss-of-function mutations in SCN5A can clinically manifest as progressive cardiac conduction disorders or as arrhythmic syndromes, such as Brugada syndrome. In addition to electrophysiological dysfunction, SCN5A mutations are also associated with myocardial fibrosis manifesting as global cardiomyopathy. In a 10-year old child exhibiting Brugada syndrome, the mutation SCN5AE555X was discovered. Therefore, cardiac sodium channelopathy pig models were generated by homologous recombination in the genetic background of outbred Yucatan minipigs via SCNT exhibiting the orthologous porcine heterozygous mutation SCN5AE558X. The heterozygous mutant animals were viable and fertile, and showed no sudden death over a 2-year monitoring period. They showed reduced SCN5A protein expression, which resulted in diminished total sodium conductance. The heterozygous mutant hearts showed slowed conduction and increased susceptibility for ventricular arrhythmias in the absence of structural defects of the myocardium or specialized conduction system. In total, a novel animal model was established for understanding the mechanisms linking sodium channel dysfunction to cardiac pathophysiology (Park et al., 2015b).
Jump up ^ PDB: 1HJ0​; Stoll R, Voelter W, Holak TA (May 1997). "Conformation of thymosin beta 9 in water/fluoroalcohol solution determined by NMR spectroscopy". Biopolymers. 41 (6): 623–34. doi:10.1002/(SICI)1097-0282(199705)41:6<623::AID-BIP3>3.0.CO;2-S. PMID 9108730. The thymosin is β9, bovine orthologue of human β10. Stabilised by organic solvent, the structure was determined by NMR. (Free β-thymosins lack a stable fold in solution)
The expression of Tβ4 mRNA is cell cycle dependent and is highest at the G0/G1 transition and during S-phase (), and changes in the expression of Tβ4 appear to be related to cell differentiation. It has been reported that hepatocyte growth factor, nerve growth factor or fibroblast growth factor (FGF) can increase the level of Tβ4 mRNA () and, in addition, interferon treatment augments the transcription of the Tβ4 gene (). It has also been shown that increased Tβ4 expression in cancer cells promotes metastasis, possibly by increasing cell mobility.
In the experiments, an epithelial wound was made in the corneas of sedated rats. A Tb4 solution was applied at several concentrations to the injured eyes in one group of rats while another group was treated with a solution without Tb4. Following 12, 24 and 36 hours, the eyes were tested by microscopic observation for epithelial growth over the injured site. Investigators found the Tb4 accelerated corneal wound repair at doses of Tb4 similar to those found to repair skin wounds. When tested 24 hours after treatment, the rate of accelerated repair was proportional to the concentration of Tb4, with the highest dose (25 microgram) showing a threefold acceleration of epithelial cell migration, compared to untreated. Treatment with Tb4 showed anti-inflammatory effects, helping resolve the injury. An application to human cells in a model of human corneal cells in culture showed that Tb4 enhanced epithelial cell migration in vitro.
5-HTP is decarboxylated to serotonin (5-hydroxytryptamine or 5-HT) by the enzyme aromatic-L-amino-acid decarboxylase with the help of vitamin B6.[40] This reaction occurs both in nervous tissue and in the liver.[41] 5-HTP crosses the blood–brain barrier,[42] while 5-HT does not. Excess 5-HTP, especially when administered with vitamin B6, is thought to be metabolized and excreted.[43][44]
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