Follistatin

Protbox
Name=Follistatin
Photo=Follistatin activin Complex.pngCaption=The Structure Of The Follistatin:Activin Complex
Gene = HUGO code: [http://www.gene.ucl.ac.uk/nomenclature/data/get_data.php?hgnc_id=HGNC:3971 FST]
Structure = [http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?form=6&db=t&Dopt=s&uid=35669 Follistatin:Activin Complex structure]
Review =
Type=Growth factor
Functions= Regulates members of the TGF beta superfamily ligands
Domains= 3 FOLN domains, 3 KAZAL domains
Diseases=polycystic ovary syndrome (PCOS)
Taxa = "Homo Sapiens"; homologs: many metazoan phyla
Cells = many, placenta, blood, ovary, liver, testis
Location = extracellular
Mods=
Names= Follistatin, FSH-Suppressing Protein, Activin-binding protein
Interactions=Activin, inhibin, BMP5
Pages=

Follistatin is a single chain autocrine glycoprotein found to be "ubiquitous" within the body of nearly all higher animals, that is the product of a single gene.

It was initially isolated from "follicular fluid" and was identified as a protein fraction that inhibited Follicle-stimulating hormone (FSH) secretion from the anterior pituitary, and so was known as "FSH-suppressing protein" (FSP). Since then its primary function has been determined to be the binding and "bioneutralization" agent of members of the TGF-beta superfamily, with primary focus on Activin, a paracrine hormone (TGF-b member) which enhances secretion of FSH in the anterior pituitary.

Biochemistry

It is part of the inhibin-activin-follistatin axis.

There are three known isoforms, FS-288, FS-300, and FS-315. Two are known to be created by alternative splicing of the primary mRNA transcript, FS-288 and FS-315. FS-300 (porcine follistatin) is thought to be the product of "post-translational" modification via truncation of the primary amino-acid chain.

Although FS is "ubiquitous" it's highest concentration has been found to be in the female ovary, followed by the skin.

In the 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.

Follistatin is involved in the development of the embryo. It has inhibitory action on bone morphogenic proteins (BMPs); BMPs induce the ectoderm to become epidermal ectoderm. Inhibition of BMPs allows neuroectoderm to arise from ectoderm, a process which eventually forms the neural plate. Other inhibitors involved in this process are noggin and chordin.

Follistatin and BMPs are also known to play a role in folliculogenesis within the ovary. The main role of follistatin in the oestrus/menstrus ovary, so far, appears to be progression of the follicle from "early antral" to "antral/dominant", and importantly the promotion of cellular differentiation of the "oestrogen" producing "granulosa cells" (GC) of the dominant follicle into the progesterone producing "large lutein cells" (LLC) of the corpus luteum.

Clinical significance

Follistatin is being studied for its role in regulation of muscle growth in mice, as an antagonist to myostatin (aka GDF-8, a TGF superfamily member) 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. cite journal |author=Lee SJ, McPherron AC |title=Regulation of myostatin activity and muscle growth |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue=16 |pages=9306–11 |year=2001 |pmid=11459935 |doi=10.1073/pnas.151270098 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=11459935] cite web |url=http://www.eurekalert.org/pub_releases/2007-08/jhmi-mm082407.php |title='Mighty mice' made mightier |accessdate=2008-02-26 |format= |work=]

It is also being investigated for its involvement in polycystic ovary syndrome (PCOS), though there is debate as to its direct role in this infertility disease.

References

External links

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