Disease relevance of Fst

• Replacement therapy with 17 beta-estradiol-3-benzoate (10 micrograms/100 g body weight) subcutaneously daily for 7 d in GDX female rats resulted in a slight further increase in follistatin mRNA levels compared to GDX females [1].
• Activin A is an autocrine activator of rat pancreatic stellate cells: potential therapeutic role of follistatin for pancreatic fibrosis [2].
• Excess activin or insufficient follistatin may contribute to T-I hyperplasia [3].
• The EST similar to rat P044, the EST similar to galectin-1, follistatin, annexin I, and the interferon-inducible gene 1-8U were also expressed in benign prostatic hyperplasia tissue [4].
• We suggest that follistatin is produced by vascular SMCs and is involved in the course of atherogenesis [5].

Psychiatry related information on Fst

• The assessment of spontaneous locomotor activity (SLA) showing a significant increase in the distance travelled was observed in the 2% and 4% methanol-exposed groups in both the FS and FD animals when compared with their respective controls, but the effect was more marked in the FD group [6].

High impact information on Fst

• Time-course studies in adult male and female rats showed that the increase in follistatin mRNA levels after GDX is rapid, with significant increases occurring within 24 h after GDX, and parallels or precedes increases in FSH beta mRNA levels and FSH secretion [1].
• To assess the potential physiologic role of follistatin in the rat pituitary, we have investigated the effects of gonadectomy (GDX) and of sex steroid replacement on pituitary follistatin gene expression [1].
• Follistatin is a glycoprotein, originally isolated from the gonads, that specifically inhibits follicle-stimulating hormone (FSH) biosynthesis and secretion [1].
• In contrast, therapy with testosterone propionate (500 micrograms/100 g body weight) subcutaneously daily for 7 d in GDX male rats resulted in a decrease in follistatin mRNA levels, towards but not completely back to baseline levels in intact males [1].
• To this end, we infused follistatin, an activin antagonist, into the portal vein of the rat [7].

Chemical compound and disease context of Fst

• A gradual loss in the body weight gain was observed in the pups exposed to 2% and 4% methanol in the FD group, while FS group exhibited this alteration only at 4% exposure [6].

Biological context of Fst

• The expression of inhibin beta A and beta B subunits, follistatin, and activin-A receptor messenger RNA (mRNAs) in different stages of rat seminiferous epithelial cycle was analyzed by in situ hybridization in order to understand their role in the regulation of spermatogenesis [8].
• Follistatin and FSH-beta gene expression in rat pituitary cultures were also measured by competitive quantitative RT-PCR and northern analysis, respectively [9].
• These results indicate that FS and activin A may act reciprocally in liver regeneration, and also suggest that activin AB and B may play roles in liver regeneration that differ from that of activin A [10].
• Transient transfection of gonadotrope-derived alphaT3-1 cells with a rat follistatin promoter-luciferase reporter plasmid reveals that PACAP stimulates follistatin gene transcription [11].
• The upregulation of cyclin D1 and follistatin mRNA at the early phase after EE administration was considered to have been affected by the upregulation of Wnt4 [12].

Anatomical context of Fst

• Inhibin beta A and follistatin mRNAs were coexpressed in stage IX-XI Sertoli cells, suggesting close interplay between these molecules [8].
• Follistatin mRNA was seen in the ovaries from 15 day pc onward and in the oviducts at 11 days postnatally [13].
• Expression of inhibin beta A and beta B, follistatin and activin-A receptor messenger ribonucleic acids in the rat seminiferous epithelium [8].
• In the present study, we examined the expression of PACAP mRNA within the paraventricular nucleus (PVN) during maturation (Days 20-60) in the male rat and compared this expression to the levels of the gonadotropin subunits, follistatin, and GnRH-receptor mRNAs within the anterior pituitary [14].
• Since PACAP and follistatin are colocalized in multiple tissues including the brain, adrenals, and gonads, our findings may reflect a broadly distributed autocrine/paracrine mechanism for modification of activin effects that is under PACAP control [11].

Associations of Fst with chemical compounds

• Expression of inhibin betaA, betaB and follistatin mRNAs in the carbon tetrachloride induced rat liver regeneration model [10].
• Regulation of inhibin beta chains and follistatin mRNA levels during rat hepatocyte growth induced by the peroxisome proliferator di-n-butyl phthalate [15].
• Crystal structures of the heparan sulfate-binding domain of follistatin. Insights into ligand binding [16].
• In addition, we have confirmed the binding of the sucrose octasulfate and D-myo-inositol hexasulfate molecules to this follistatin domain and determined the association constants and stoichiometries of both interactions in solution using isothermal titration calorimetry [16].
• To gain a structural insight into this interaction, we have solved the crystal structure of the presumed heparan sulfate-binding domain of follistatin, both alone and in complex with the small heparin analogs sucrose octasulfate and D-myo-inositol hexasulfate [16].

Regulatory relationships of Fst

• Evidence that PACAP and GnRH down-regulate follicle-stimulating hormone-beta mRNA levels by stimulating follistatin gene expression: effects on folliculostellate cells, gonadotrophs and LbetaT2 gonadotroph cells [9].
• These experiments suggest a mechanism by which PACAP influences FSH production selectively by an autocrine effect on gonadotrophs and by a paracrine mechanism through folliculostellate cells that involves follistatin [9].
• Gonadotropin-releasing hormone pulse frequency regulates expression of pituitary follistatin messenger ribonucleic acid: a mechanism for differential gonadotrope function [17].
• Activin raised basal as well as FSH-stimulated steady-state follistatin mRNA levels up to ten- and twofold above controls respectively, whereas epidermal growth factor was found to inhibit FSH-stimulated follistatin mRNA levels in a dose-dependent manner [18].
• Follistatin can inhibit PSC activation and collagen secretion by blocking autocrined activin A and decreasing TGF-beta expression and secretion of PSCs [2].

Other interactions of Fst

• These results indicate that the growth stimulatory action of peroxisome proliferators may be mediated via the decrease in activin A level and activity and suggest that the increases in follistatin as well as inhibin betaB and betaC chains may play a role in peroxisome proliferator-stimulated hepatocyte growth [15].
• Gonadotropin-releasing hormone regulates follicle-stimulating hormone-beta gene expression through an activin/follistatin autocrine or paracrine loop [19].
• Regulation of luteinizing hormone-beta and follicle-stimulating hormone (FSH)-beta gene transcription by androgens: testosterone directly stimulates FSH-beta transcription independent from its role on follistatin gene expression [20].
• Follistatin associates with transforming growth factor-beta-like growth factors such as activin or bone morphogenetic proteins to form an inactive complex, thereby regulating processes as diverse as embryonic development and cell secretion [16].
• Both males and females expressed the follistatin, inhibin alpha, and betaB mRNAs, whereas the betaA mRNA was not detected [21].

Analytical, diagnostic and therapeutic context of Fst

• Competitive reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of total pituitary follistatin mRNA revealed no significant changes; however, semiquantitative RT-PCR analyses revealed the presence of two follistatin mRNA species, one of which, corresponding to follistatin-288, was developmentally regulated [14].
• In the present series of experiments we demonstrate that PACAP-induced suppression of FSHbeta mRNA correlates with a rise in follistatin mRNA levels in primary pituitary cell cultures [11].
• Pituitary FS mRNA increased rapidly after castration, with levels rising 3-fold by 12 h and 4-fold by 36 h when compared to intact animals (P < 0.05) [17].
• 1) Two weeks after ovariectomy, rat pituitary FS mRNA levels increased substantially (4.09-fold vs. intact) with a modest increase in beta B-inhibin mRNA levels (1.88-fold vs. intact) [22].
• A 337-basepair fragment of the follistatin cDNA was amplified by polymerase chain reaction from a rat ovarian cDNA library and subcloned into pGEM3 [23].

References