Androgens come to the rescue of anxiety and depression: Testosterone, a male reproductive steroid hormone, decreases PHF8 levels, increases the expression of serotonin receptors Htr1a and Htr2a, and promotes resistance to stress-induced -anxiety and -depression, via down-regulation of its target gene, 10/August/2018, 9.45 am

Introduction: What they say: 

A study from Department of Molecular Biology, Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA; and Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA shows that “Phf8 loss confers resistance to depression-like and anxiety-like behaviors in mice.” This research paper was published, in the May 2017 issue of the journal “Nature communications” [One of the best research journals in Metabolism with an I.Fs of ], by Prof.Hochedlinger K, Ryan M. Walsh and others.

What we say: 

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that:  Androgens come to the rescue of anxiety and depression: Testosterone, a male reproductive steroid hormone, decreases PHF8 levels, increases the expression of serotonin receptors Htr1a and Htr2a, and promotes resistance to stress-induced -anxiety and -depression, via down-regulation of its target gene

From the significance of the study to Public health relevance:

Given that: (1) one in three suffer from anxiety-related disorders worldwide; (2) nearly 12% of world population suffer from anxiety-related disorders in any given year; (3) 5-30% of people suffer from anxiety at some point in their lives; (4) 40 million adults in the US suffer from anxiety disorders; (5) nearly $42 billion a year spent in the US to treat anxiety disorders; (6) anxiety and depression are associated with higher rate of morbidity; (7) the percentage of people who suffer from anxiety is more from developed countries than from developing countries, while the opposite is true with depression; and (8) the global economic cost spent in the treatment of anxiety and depression occupies the significant portion of health care bill, there is an urgent need to find: (i) a way to cure  long term anxiety and depression that are leading to a number of serious health complications; (ii) a way to induce resilience to anxiety and depression; (iii) a cheaper alternative to the existing expensive drugs; and (iv) a side-effect-free Natural product-based drug that not only alleviates, but also cures anxiety and depression.

What is known?

Mutations in PHF8, a histone demethylase, has been shown to result in cognitive defects and cleft lip/palate. However, its role in other physiological processes remains to be determined.

Prof.Hochedlinger Konrad’s research team has recently shown that knocking out PHF8/JMJD1.2 in mice results in: (1) no cognitive impairment; (2) up-regulation of serotonin receptors Htr1a and Htr2; (3) normalization of Serotonin signalling; and (4) resistance to stress-induced anxiety- and depression-like behaviour, suggesting that inhibiting the expression of PHF8 may aid in the treatment of anxiety and depression.

From research findings to Therapeutic opportunity:

A number of studies suggest that Testosterone may play a role in anxiety and depression. However, the mechanistic basis of which remains largely unclear. This study provides, for the first time, mechanistic insights into how a male reproductive hormone Testosterone may attenuate anxiety and depression.

Testosterone, by increasing the expression of its target gene, it may decrease the expression of PHF8. Thereby, it may: (1) increase the expression of genes involved in serotonin signaling such as Htr1a and Htr2a; (2) normalize serotonin signaling; (3) promote resistance to stress-induced anxiety, and (4) heighten resistance to stress-induced depression-like behavior. Thus, pharmacological formulations encompassing “Testosterone  or its analogs, either alone or in combination with other drugs, may be used to treat anxiety and depression; and promote resistance to depression- and anxiety-like behaviors (fig 1).[easy_payment currency=”USD”]

Figure1. Mechanistic insights into how Testosterone decreases PHF8 levels, increases serotonin receptors Htr1a and Htr2a levels and promotes resistance to depression-like and anxiety-like behaviors

Given the mechanistic basis of how testosterone may function as an anti-depressive agent,  physicians and psychologists may consider: treating their needy patients with testosterone or beginning a clinical trial.  

Figure 2. The chemical structure of Testosterone. Testosterone functions as an anti-depressive agent through up-regulation of its target genes

Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by Dr L Boominathan Ph.D.

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Amount: $ 500#

Undisclosed mechanistic information: How testosterone decreases PHF8 levels, increases serotonin receptors Htr1a and Htr2a levels and promotes resistance to stress-induced anxiety and depression.

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References:

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Citation: Boominathan, L., Androgens come to the rescue of anxiety and depression: Testosterone, a male reproductive steroid hormone, decreases PHF8 levels, increases the expression of serotonin receptors Htr1a and Htr2a, and promotes resistance to stress-induced -anxiety and -depression, via down-regulation of its target gene, 10/August/2018, 9.45 am, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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