A focus on Follistatin…

Many of the markers Ansh Labs develops are novel and very early in their lifecycle. There is a growing body of research that supports clinical diagnostic utility for the assays we have developed, and there is exciting putative research involving the biomarkers that are in our research and development pipeline. Some of the assays are still so new that they may not be recognized by select regulatory bodies as clinical in vitro diagnostic assays at the present time.
Follistatin is an autocrine glycoprotein that is expressed in nearly all tissues of higher animals.  Its primary function is the binding and bioneutralization of members of the TGF-β superfamily, with a particular focus on activin, a paracrine hormone.Follistatin interests us because there are multiple interesting areas in which it is being researched:  Muscle Growth, Inflammation/wound healing, folliculogenesis, PCOS, Cancer.
Muscle Growth- Follistatin is being studied for its role in regulation of muscle growth in mice, as an antagonist to myostatin (GDF-8) which inhibits excessive muscle growth. Lee & McPherron demonstrated that inhibition of GDF-8, either by genetic elimination (knockout mice) or by increasing the amount of follistatin, resulted in greatly increased muscle mass which may have applications for promoting muscle growth in human disease settings as well as in livestock animals.

Recommended Reading:

Inflammation and Wound Healing – In tissues activin has a strong role in cellular proliferation, thereby making follistatin the safeguard against uncontrolled cellular proliferation and also allowing it to function as an instrument of cellular differentiation. Both of these roles are vital in tissue rebuilding and repair, and may account for follistatin’s high presence in the skin. In the blood, activin and follistatin are both known to be involved in the inflammatory response following tissue injury or pathogenic incursion. The source of follistatin in circulating blood plasma has yet to be determined, but due to its autocrine nature speculation suggests the endothelial cells lining all blood vessels, or the macrophages and monocytes also circulating within the whole blood, may be sources.

Recommended Reading:

Folliculogenesis- A major role of follistatin is the binding and biological neutralization of activins and other members of the TGF-Beta superfamily of hormones.  In folliculogenesis, follistatin regulating activity appears to be important for the progression of the follicle from early antral to antral/dominant phase, and Follistatin regulates granulosa cell function resulting in luteinization or atresia by promoting the differentiation of the estrogen-producing granulosa cells of the dominant follicle into the progesterone-producing large lutein cells of the corpus luteum.

Recommended Reading:

PCOS – Eldar-Geva et al reports that since Follistatin neutralizes Activin bioactivity, a decrease in the ratio of Activin to Follistatin could encourage characteristic features of PCOS. However, there is debate as to its direct role with PCOS and more research is needed.

Recommended Reading:

Cancer – More recent research suggests that Follistatin may have a role in prostate cancer progression and ovarian cancer particularly when combined with CA-125 to reduce false positive results.

Recommended Reading:

Page References:

Wikipedia contributors. “Follistatin.” Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 2 Mar. 2013. Web. 4 Apr. 2013.

 

Mobile Phone Wallpapers of Ribbon Structures

Everyone loves neat wallpapers, right? We would like to share some ribbon structures that Dr. Marko Hyvonen of the University of Cambridge has developed for Follistatin, Inhibin and Activin. These images are sized for mobile phones (we are working on tablet sized images): http://www.anshlabs.com/graphic-images/ In case you need a larger resolution for a presentation, let us know!

Boy or Girl? Beyond X and Y

Boy or Girl? Beyond X and Y

Insulin and insulin-like growth factors (IGFs) are hormones known for their role in metabolism and growth, but now scientists are elucidating their importance in another arena: sex determination. Researchers at the University of Geneva (UNIGE) found that in the absence of these factors at the time of sex determination, embryos do not differentiate into either male or female and have no adrenal glands.

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To analyze the impact of these hormones on sex determination, the group used genetically modified mice. The scientists genetically inactivated the receptors for insulin and IGFs in mouse embryos. This led to reduced proliferation rate of somatic progenitor cells in both XX and XY gonads prior to sex determination, together with the downregulation of hundreds of genes associated with the adrenal, testicular, and ovarian genetic programs. As such, the embryo and its gonads remained stuck in a fully undifferentiated state for several days.

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The authors explain that embryos lacking functional insulin/IGF signaling exhibit (i) complete agenesis of the adrenal cortex, (ii) embryonic XY gonadal sex reversal, with a delay of Sry upregulation and the subsequent failure of the testicular genetic program, and (iii) a delay in ovarian differentiation so that mutant gonads, regardless of genetic sex, remained in an extended undifferentiated state before the ovarian differentiation program ultimately is initiated at around embryonic day 16.5. These findings demonstrated the essential role of these hormones and growth factors in sexual differentiation, the authors report.

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The study was published in PLOS Genetics, in an article titled “Insulin and IGF1 Receptors Are Essential for XX and XY Gonadal Differentiation and Adrenal Development in Mice”.

 

 

 

Study Debunks ‘Andropause’ in Aging Men

Study Debunks ‘Andropause’ in Aging Men

In this article by Bruce Jancin of the Clinical Endocrinology News Digital Network, the often discussed age-related decline in testosterone and popularized concept of ‘andropause” is rejected. In a study of 1,382 males approximately 54 years of age who were followed over 5 years, testosterone levels did not decrease significantly. What was interesting about the analyses is that lower testosterone seems to be an important indicator of the overall health status of older males. One of the important preventive measures is to keep fit and to avoid putting on excessive weight.

Depression during pregnancy tied to premature births

Depression during pregnancy tied to premature births

Amy Norton discusses a study in which researchers analyzed 14,000 pregnancies to determine the incidence of preterm deliveries that occurred in women who screened positive for clinical depression during pregnancy. While only 14% of women who screened positive for depression delivered preterm, 10% of women who did not screen positive still delivered earlier than the 37th week. Depression is considered a risk factor for preterm delivery, but there is still more to understand about the cause and effect of pre-term delivery.

NIH researchers implicate unique cell type in multiple sclerosis

NIH researchers implicate unique cell type in multiple sclerosis

Researchers at NIH found evidence of a unique cell, which contributes to the progression of MS. This discovery may affect how drugs will be evaluated, and possibly the importance of utilizing certain diagnostic markers in the future treatment of MS patients. It may also open the door for more clinical trials of new classes of drugs as a primary or complementary treatment of MS and other autoimmune disorders.

Fertility hope following Chemotherapy and Radiation for Cancer patients

Fertility hope following Chemotherapy and Radiation for Cancer patients

Researchers from Walter and Eliza Hall Institute, Monash University, and Prince Henry’s institute of Medical Research have identified two specific proteins called PUMA and NOXA that cause egg cell death in the ovaries. When DNA of the egg cells are damaged following chemotherapy or radiation, PUMA and NOXA trigger cell death rendering female cancer patients infertile. Cell death is a necessary response to DNA damage to maintain general health, but this observation led to an unexpected discovery. When egg cells are missing PUMA and NOXA proteins, the cells not only survive irradiation but are able to repair their DNA. This discovery may lead to therapies aimed at preventing egg cell death in cancer patients and maintaining their reproductive health.

Increased risk of Dementia among the elderly using Benzodiazepines

Increased risk of Dementia among the elderly using Benzodiazepines

A positive correlation has been found between chronic users of Benzodiazepines and dementia by researchers at Universite’ Bordeaux Segalen in France. Benzodiazepines are commonly prescribed in most countries to treat anxiety and insomnia for short periods of time, particularly among the elderly. Despite good practices and guidelines, many people take them for extended periods of time and that’s when they say problems occur. This study was conducted over a period of 20 years on 1,063 men and women over 65 and concluded that an increased risk of dementia leading to serious falls and fractures exists when Benzodiazepines were used for a long periods of time. Moving forward, chronic use of Benzodiazepines should be limited and cautioned against the elderly.

Can an Anti-depressant be prescribed for heart failure?

Can an Anti-depressant be prescribed for heart failure?

John Tesmer and his team at the University of Michigan say they might be able to. Paroxetine, a selective serotonin reuptake inhibitor (SSRI), sold under the name of Paxil, inhibits a protein kinase (GRK2) that over expresses during heart failure. While Paxil is commonly used to help treat depression and anxiety disorders all over the world, it may now be a tool to treat heart failure. GRK2 becomes increasingly expressed as the strength of the heart’s contractions weakens. They found that Paroxetine improved the strength of the heart’s contractions in an animal model without interfering with the heart rate. During a screening of FDA approved drugs that inhibit GRK2, they found that Paroxetine binds and inhibits the activity of GRK2. While Paxil is commonly used to help treat depression and anxiety disorders, investigators may explore its efficacy as a treatment for certain heart diseases.