Rapid Communication - Journal of Clinical Endocrinology Research (2022) Volume 5, Issue 5
Potential methodologies of intervention for compounds that modify endocrine hormones
Department of Biology, Norwegian University of Science and Technology, Høgskoleringen, Norway
- *Corresponding Author:
- Mark Augustine
Department of Biology
Norwegian University of Science and Technology
Received: 05-Oct-2022, Manuscript No. AAJCER-22-80576; Editor assigned: 07-Oct-2022, PreQC No. AAJCER-22-80576 (PQ); Reviewed: 21-Oct-2022, QC No. AAJCER-22-80576; Revised: 24-Oct-2022, Manuscript No. AAJCER-22-80576 (R); Published: 31-Oct-2022, DOI:10.35841/aajcer-5.5.125
Citation: Augustine M. Potential methodologies of intervention for compounds that modify endocrine hormones. J Clin Endocrinol Res. 2022;5(5):125
The term "endocrine-disrupting chemicals” refers to substances that mimic or inhibit the transcriptional activation caused by naturally occurring steroid hormones by attaching to steroid hormone receptors. edc are substances that, according to the food quality protection act of 1996, "may have an impact in humans that is analogous to an effect generated by a naturally occurring oestrogen, or other such endocrine action as the administrator may designate." later, those that act on the oestrogen, androgen, and thyroid hormone receptors were included to the criteria. Through the inhibition of histone deacetylase activity and the stimulation of mitogen-activated protein kinase activity, xenobiotics and environmental pollutants can serve as hormone sensitizers. On DNA methylation state, some endocrine disruptors may have genome-wide impacts.
Endocrine, Androgen, Histone deacetylase, Endocrine-disrupting chemicals.
Because reliable studies demonstrate the presence and absence of low-dose effects using the same chemicals and experimental models, the problem is still open and the area is prime for further research. It is important to keep in mind, nevertheless, that the reality of low dosage effects is becoming acknowledged. Additionally, there is dispute regarding the level of danger associated with exposure to endocrine-disrupting substances. According to estimates, this risk could be catastrophic. This is the first instance that comes to mind of a ligand behaving as an antagonist on an orthologous nuclear receptor in a different species while working as an agonist on a particular nuclear receptor in a different species. The obvious inference is that using data collected in rats to predict the danger of human exposure to these PCBs or combinations that contain them will likely lead to incorrect conclusions because rats are the principal pharmacological and toxicological model organism. Another potential method of endocrine disruption is interference with the metabolism of naturally occurring steroid hormones, bioactive dietary substances, and xenobiotics that are normally mediated by SXR/PXR. This is demonstrated by the ability of xenobiotics, such as these PCBs, to block activation of SXR/PXR.
Endocrine disruption by modulating co-activators of nuclear receptors
Nuclear receptors bring a group of coactivator proteins and the basic transcriptional machinery to the regulatory region of target genes where they bind directly to hormone response elements to initiate transcription . The p160 family includes coactivators. the thyroid hormone receptor activator protein 220/vitamin d receptor-interacting protein 205/peroxisome proliferator-activated receptor binding protein, which lacks intrinsic histone acetyl transferase activity, and the transcriptional intermediary factor 2 glucocorticoid receptor interacting protein 1 and activator of thyroid and retinoic acid receptor amplified in breast cancer, which have intrinsic histone acetyl transferase activity nuclear receptor activation is regulated by tissue-specific variations in coactivator levels as well as by general competition among nuclear receptors and other transcription factors for coactivators.
Hormone sensitizers acting as endocrine disrupters
An innovative method of endocrine disruption has been shown by recent research by Jansen and colleagues . Their findings demonstrate that xenobiotic short-chain fatty acids like valproic acid and methoxyacetic acid (MAA) do not resemble endogenous hormones instead they increase hormone receptor activity via changing cell signals that activate protein kinases or block histone deacetylases . Exposure to these short-chain fatty acids increased cellular sensitivity to oestrogens, progestin, and other nuclear hormone receptor ligands and enhanced the transcriptional efficacy of ligand-activated nuclear hormone receptors in vitro and in vivo.
Obesogens that impact endocrine function
Developmental or chronic lifetime exposure to TBT and other organotins could act as chemical stressors or obesogens that activate RXR and/or RXR: pparγ signaling to promote long-term changes in adipocyte number and/or lipid homeostasis . The effects of EDC on other nuclear receptors that modulate lipid metabolism, such as pparα, liver X receptor, and farnesoid X receptor, remain largely unexplored, making this a hot topic for future investigation .
The improper modulation of ER, AR, and thyroid hormone receptors has previously been linked to endocrine disruption. The examples of endocrine disruption discussed above highlight the complexity of ligand-activated nuclear receptor transcription and point to numerous potential targets for xenobiotic disruption of endogenous hormone signalling. Underappreciated as potential pathways for endocrine disruption are mechanisms involving the potential disruption of hormone metabolism, receptor protein degradation, sensitization by short-chain fatty acid exposure, altered DNA methylation, and effects on receptors other than ER, AR, and thyroid hormone receptor. A few nuclear hormone receptors' activity has been directly impacted by endocrine disruptors discovered by genomic screening and molecular modelling. Increased involvement in the study of EDC action by biomedical scientists not normally working in this area, particularly those specializing in signalling, hormone action, and transcriptional regulation, will be key to our future understanding of endocrine disruption and its potential consequences for humans and wildlife.
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