User:Arizzo0226/sandbox

Article Evaluation

For this assignment, I decided to evaluate the article on hypothyroidism. After reviewing the article, I was pleasantly surprised by the organization of the article itself. I thought that it followed a very logical order and that the main endocrinology concepts were paired with great visuals to help readers understand the content. I believe there is room for improvement in the figure captions describing symptoms of patients with the condition. I noticed grammar mistakes and missing punctuation. While many of the sources were fairly recent publications, I noticed that the information regarding Myxoedema were older. The two sources used for this content were published in 1891 and 1892. Thus, if I were editing this article I would try to find more up-to-date sources. The overall tone of the article was neutral and informative; there were no signs of personal opinion ined the writing. After reading the article I viewed the talk page to see what conversation was taking place regarding the content and layout. The last advertised edits to the article were made in April 2017. Some of the discussion taking place seems to revolve around finding more adequate sources to support the information presented by the authors.

Potential Articles

1) Carbimazole: The article could be improved by finding more sources. This article has not been verified by Wikipedia yet because the author did not cite the information used. I find this topic interesting and would like to know more about its course of action and how it is used as a treatment for hyperthyroidism. Additionally I think showing a diagram of how the drug interacts with thyroid peroxidase would be useful to readers. Visuals typically help with understanding complex biological processes.

2) Jod-Basedow Phenomenon: The article could be improves by finding more sources. It appears that the author only used one source. I have heard of thyroid problems when too much iodine is taken by an individual. I believe that the thyroid can become dysfunctional if too much iodine is introduced. Including more about why this phenomenon happens, what research has been done on the topic, and potential implications would improve this article drastically. This is definitely something I am interested in moving forward.

3) Thyroid Hormone Receptor: This article may indeed be what I ultimately land on editing. I love finding out more on receptors and the way that they word, so this is definitely intriguing to me. This article needs more information on the differences between receptor types. Additionally, it could benefit largely from additionally sources and more images showing hormone action at the level of the receptors themselves. As it stands, there are not any sources citing the information on the receptors in their active or inactive states. This is likely a large contributor to why the article has not officially been published on Wikipedia.

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ARTICLE TO DO LIST:

-Function section needs more sources and more information in general

-Mechanism of action would be improved with a visual

-Isoforms section needs more information on each subtype

-Disease linkage needs more sources and more information; could also benefit from visuals of potential symptoms

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The thyroid hormone receptor (TR) is a type of nuclear receptor that is activated by binding thyroid hormone. TRs act as transcription factor s, ultimately affecting the regulation of gene transcription and translation. These receptors also have non-genomic effects that lead to second messenger activation, and corresponding cellular response.

Structure
There are four domains that are present in all TRs. Two of these, the DNA-binding (DBD) and hinge domains, are involved in the ability of the receptor to bind hormone response elements (HREs). TRs also have a ligand binding domain (LBD) that allows them to bind to thyroid hormone with high affinity. The fourth domain is a transactivation domain which allows the receptor to bind transcription factors.

Function
Thyroid hormone receptors play critical roles in the regulation of metabolism, heart rate, and development of organisms. TRs are also involved in cell viability, and are believed to have other non-genomic affects that are currently being investigated.

Mechanism of action
Thyroid hormone can have genomic or non-genomic effects. The genomic signaling pathway directly influences gene transcription and translation, while the non-genomic pathway involves more rapid, cellular changes.

Genomic Signaling Pathway

Thyroid hormone receptors regulate gene expression by binding to hormone response elements (HREs) in DNA either as monomers, heterodimers with retinoid X receptor (RXR; which in turn is activated by binding to 9-cis-retinoic acid) or as homodimers. However TR/RXR heterodimers are the most transcriptionally active form of TR.

In the absence of hormone, TR in complex with corepressor proteins bind to HREs in a transcriptionally inactive state. Binding of thyroid hormone results in a conformational change in TR which displaces corepressor from the receptor/DNA complex and recruitment of coactivator proteins. The DNA/TR/coactivator complex then recruits RNA polymerase that transcribes downstream DNA into messenger RNA and eventually protein that results in a change in cell function.

Non-genomic Signaling Pathway

Non-genomic TR signaling is still being investigated, however, TR-α1 (a specific isoform of TR) has been linked to cell viability. The cytoplasmic function of this receptor involves a rise in cGMP concentration and the corresponding activation of protein kinase G.

Isoforms
There are two main classes of the thyroid hormone receptor, alpha and beta. The localization of these subtypes, summarized in Table 1, is largely dependent upon post-translational splicing. Genes on chromosomes 3 and 17 are transcribed and translated into c-erbA gene products. Splicing of these gene products leads to the production of different isoforms. There are three TR-α receptor splice variants encoded by the THRA gene and three TR-β isoform splice variants encoded by the THRB gene. Of these variants, thyroxine is only able to bind to four of them: TR-α1,TR-β1,TR-β2, and TR-β3.

Disease linkage
Certain mutations in the thyroid hormone receptor are associated with thyroid hormone resistance. Mutations in the THRB gene can change the shape of the TR binding site, lowering its affinity for thyroid hormone. This change in affinity can have detrimental effects on metabolism, growth, and development.