Hormone Paper: Serotonin
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Hormone Paper: Serotonin
Serotonin, also known as 5-hydroxytryptamine, functions in the central nervous system as a neurotransmitter and the periphery as a hormone (Swami &Weber, 2018). It is mostly produced in the digestive system; however, some is produced by the nervous system and platelets. The hormone is made from tryptophan amino acid, an essential amino acid obtained from the diet (Pozhidaev et al., 2020). The 5-HT targets various physiologic controllers, including steroids, neurotrophic factors, and gene transcription modulators. It plays a crucial role in modulating numerous brain functions such as mood regulation, learning and memory, sleep, and sensory functions. This paper will discuss serotonin synthesis, signaling cascades, target cells/ systems, functions, and associated diseases when the hormone is deregulated. The report will also propose a new research topic on unique aspects of the hormone and methods used in the study.
Synthesis
Serotonin is synthesized via a multistep pathway, which involves two significant enzymes; amino acid decarboxylase and tryptophan hydroxylase. The L- tryptophan is converted by tryptophan hydroxylase enzyme to L-5OH-tryptophan, converted to serotonin by amino acid decarboxylase. 90% of 5-HT is synthesized in the gastrointestinal tract; however, it is also synthesized in the brain since it cannot cross the blood-brain barrier (Shireen, 2016). The rate-limiting enzyme in serotonin synthesis is the tryptophan hydroxylase. Monoamine oxidase A metabolizes serotonin to 5-hydroxy indole acetic acid, whose concentration in the cerebrospinal fluid reflects serotonin activity in the central nervous system. The tryptophan hydroxylase enzyme exists in two different forms, Tryptophan hydroxylase 1 and 2. Tph1 is mainly expressed in the gastrointestinal tract enterochromaffin cells, while Tph2 is expressed fully in the brainstem’s serotogenic neurons. Tph1 is responsible for serotonin presence in the bloodstream, while Tph2 is responsible for serotonin production in the brain. The brain-derived serotonin is a neurotransmitter, while the gut-derived serotonin is a hormone that controls various body processes (Herr &Duerschmied, 2017).
Signaling Cascades
Serotonin floats in the cytosol of serotoninergic neurons initially. Upon signaling, the hormone is transported by vesicular monoamine transporters into the synaptic vesicles of presynaptic neurons, releasing neurotransmitters to the synaptic cleft. The binding receptors of 5-HT are divided into seven groups based on signaling and conserved structures. The groups include the G-protein coupled serotonin receptors, the ionotropic serotonin receptors, serotonin 1, 2, 5, and 4/5/6 receptors (Shireen, 2016). The serotonin receptors 1 and 5 inhibit adenylyl cyclase through G-protein, preventing cyclic adenosine monophosphate accumulation. Cyclic AMP signals intracellular transduction in organisms. The 5-HT1 triggers the phospholipase pathway, which generates messengers for diacylglycerol and inositol 1, 4, 5- triphosphate (1P3).
Calcium ion stores in the endoplasmic reticulum are mobilized by 1P3 and DAG, resulting in activation of calmodulin/calcium-dependent kinases. The kinases phosphorylate proteins that control the operation of cells. The 5-HT1B autoreceptors suppress the excessive release of 5-HT1. The 5HT2 receptors are coupled via G-proteins to catalyze the phosphorylase pathway, which in turn hydrolyses phosphatidylinositol bisphosphate into DAG, 1P3, and phosphorylase A (Pozhidaev et al., 2020). Adenylyl cyclase couples the 5-HT4/6/7 receptors using the G-protein, resulting in increased intracellular cyclic AMP levels in postsynaptic neurons, hence activating the protein kinase A pathway. Activation of the 5-HT4/6/7 receptors by serotonin regulates neuronal excitability, synaptic transmission, and neuroprotection. The ionotropic 5-HT3 receptors for serotonin don’t require G- proteins and second messengers since their structure is surrounded by ion channels permeable to sodium, potassium, and calcium ions. When serotonin neurotransmitters are bound to the ionotropic receptors, it results in neural excitability (Welford et al., 2016).
Target Cell Types/ Systems
The hormone targets the gastrointestinal tract enterochromaffin cells and the brain’s raphe nuclei cells. However, serotonin also targets the body’s immune cells and the whole body system. The body’s immune cells express serotonin synthesis enzymes, serotonin transporter, and receptors (Herr &Duerschmied, 2017).
Functions
The presence of serotonin in the brain regulate happiness, anxiety, and mood, hence low levels of the hormone are associated with depression. Serotonin present in the gut control bowel movements. The hormone is released by blood platelets and stimulates the healing of wounds. Also, it causes narrowing of arteries, hence helping in blood clotting. High levels of the hormone are associated with low libido and vice versa. The hormone helps in maintaining bone health; however, high levels lead to osteoporosis. The hormone causes nausea and is responsible for sleep (Shireen, 2016).
Impairment When Deregulated/ Associated Diseases
Deficiency of serotonin is associated with a range of psychological and physical symptoms; however, its role in psychological symptoms is not well understood (Welford et al., 2016). The hormone deficiency may be due to low tryptophan levels or deficiency of vitamins B6 or vitamin D, which are required to produce serotonin. Deficiency may also result from fewer receptors of serotonin or poor absorption after a breakdown. Low serotonin levels are associated with physiological signs such as nausea, weight gain, carbohydrate cravings, and constipation, and irritable bowel syndrome. Deficiency also leads to psychological symptoms such as depression, impulsive behavior, irritability, insomnia, poor memory, and aggression (Swami &Weber, 2018). Excessive accumulation of serotonin in the body leads to a condition known as serotonin syndrome, which results from the use of certain medications or a combination of medications. The symptoms associated with high levels of serotonin include diarrhea, headache, confusion, shivering, restlessness, high blood pressure, among others. The severity of the syndrome leads to seizures, loss of consciousness, irregular heartbeat, and high fever.
Conclusion
Serotonin is a neurotransmitter in the nervous system and a hormone in the periphery. The hormone plays a crucial role in integrating physiologic and psychological processes. A lot of research on the hormone has been carried out on serotonin’s physiological functions; however, fewer studies have been performed on the hormone’s psychological role (Herr & Duerschmied, 2017). More research should be done to show the contribution of the hormone to psychological behaviors.
Research Topic
Since the contribution of serotonin deficiency in psychological disorders is not well understood, my research paper will study the role of 5-HT receptors in controlling tardive dyskinesia using genotypes of schizophrenia patients. Tardive dyskinesia is an involuntary disorder that is a side effect of the use of antipsychotic drugs. The condition involves limb-truncal and orofacial components (Shireen, 2016). The tardive dyskinesia clinical picture and its course is not clearly defined in clients managed using antipsychotic medications.
Methods
The study will use randomized clinical trials of schizophrenia Caucasian patients who have been on psychotic drugs for three months and aged between 18-75 years old. The diagnosis for schizophrenia will be based on the tenth revision of the International Classification of Diseases (Swami &Weber, 2018). The study will exclude non-Caucasian schizophrenia patients by appearance, either Khakassians or Mongoloid with underlying acute or unstable physical disorders or brain disorders such as Parkinson’s disease or epilepsy. The experiments will be conducted following the world medical association code of ethics and approved by the mental health institute’s local bioethics committee. Blood samples for DNA analysis will be obtained using antecubital venipuncture, and genotyping will be carried without information on the patient’s medical status.
References
Herr, N., Bode, C., & Duerschmied, D. (2017). The effects of serotonin in immune cells. Frontiers in cardiovascular medicine, 4, 48.
Pozhidaev, I. V., Paderina, D. Z., Fedorenko, O. Y., Kornetova, E. G., Semke, A. V., Loonen, A. J., & Ivanova, S. A. (2020). 5-Hydroxytryptamine receptors and tardive dyskinesia in schizophrenia. Frontiers in Molecular Neuroscience, 13, 63.
Shireen, E. (2016). Experimental treatment of antipsychotic-induced movement disorders. Journal of experimental pharmacology, 8, 1.
Swami, T., & Weber, H. C. (2018). Updates on the biology of serotonin and tryptophan hydroxylase. Current Opinion in Endocrinology & Diabetes and Obesity, 25(1), 12-21.
Welford, R. W., Vercauteren, M., Trébaul, A., Cattaneo, C., Eckert, D., Garzotti, M., & Nayler, O. (2016). Serotonin biosynthesis as a predictive marker of serotonin pharmacodynamics and disease-induced dysregulation. Scientific reports, 6, 30059.