Follistatin

Background and objectives: Blood flow restriction training (BFRT) has gained substantial interest due to the lower required intensity, which may be beneficial for individuals who are not able to lift heavy weights. Therefore, we aimed at evaluating effects of 12 weeks of resistance training with and without blood flow restriction on follistatin (FST) concentrations and physical performance in elderly females. Methods: Thirty elderly female were randomly assigned into the following groups: resistance training with blood flow restriction (BFRT; n=10), resistance training without blood flow restriction (WBFRT; n=10) and control (n=10). The resistance training was carried out three session a week for 12 weeks. Serum concentrations of FST, muscular endurance and dynamic balance were assessed at baseline and after the 12week intervention. Results: Significant main effects of time were observed for FST (p =0.03, η2 = 0.15), muscular endurance (p = 0.00, η2 = 0.59) and dynamic balance (p=0.00, η2 = 0.57). FST [BFRT= 1.4 ng/ml (effect size Cohen's {d} =-0.8) significantly increased only in BFRT group. However, muscular endurance [BFRT= 95 (d=-4.1) and WBFRT = 32 (d=-0.9)] significantly increased in both intervention groups (P<0.05). In addition, dynamic balance [BFRT=-0.5 seconds (d= 2.2)] significantly increased only in the BFRT group (P<0.05). Conclusion: BFRT was able to increase FST concentrations. Due to its mechanistic role in muscle mass alterations, elderly females can incorporate our BFRT protocol to improve anabolic conditions for muscular adaptations.

Follistatin has been isolated from human placenta and has been identified in human foetal membranes and fluids. Serum follistatin levels in women rise during pregnancy particularly near term. In this study, we examined the effect of induction and stage of labour on maternal plasma concentrations of follistatin. Women who gave birth after a normal pregnancy were retrospectively divided into three groups: those who went in labour spontaneously (n = 33), needed induction by amniotomy and IV oxytocin (n = 18) or underwent planned caesarean section (n = 10). Serum was collected at 38–40 weeks of gestation, periodically through labour with a vaginal examination and once within 36 h postpartum and assayed for oestradiol, progesterone, prolactin and C-reactive protein. Follistatin was measured using a rabbit antiserum (#204) raised against purified 35 kDa bovine follistatin. Human recombinant follistatin was used as both standard and tracer. Concentrations of follistatin at 38–40 weeks of g...

Current genetic data are equivocal as to whether goat domestication occurred multiple times or was a singular process. We generated genomic data from 83 ancient goats (51 with genome-wide coverage) from Paleolithic to Medieval contexts throughout the Near East. Our findings demonstrate that multiple divergent ancient wild goat sources were domesticated in a dispersed process that resulted in genetically and geographically distinct Neolithic goat populations, echoing contemporaneous human divergence across the region. These early goat populations contributed differently to modern goats in Asia, Africa, and Europe. We also detect early selection for pigmentation, stature, reproduction, milking, and response to dietary change, providing 8000-year-old evidence for human agency in molding genome variation within a partner species.

Background and objectives: The present study was designed to determine the effect of blood flow restriction training (BFRT) on follistatin to myostatin ratio, body composition and anaerobic power of trained volleyball players. Methods: Eighteen trained volleyball players were randomly assigned into two study groups: resistance training with blood flow restriction (BFRT; n=9) and resistance training without blood flow restriction (WBFRT; n=9). The subjects performed trainings three sessions a week, for eight weeks. In each session, barbell squat, leg extension, leg curl and dumbbell lunges were performed in three sets of 15 repetitions, with rest intervals of 30 seconds. Serum follistatin and myostatin concentrations, body composition and anaerobic power were assessed before and after the study. Data were analyzed using the paired sample t-test, Wilcoxon test, independent sample t-test and Mann-Whitney U test. All statistical analyses were done in SPSS (version 22), and a P-value of less than 0.05 was considered statistically significant. Results: Follistatin levels increased significantly (P=0.001), while myostatin levels decreased significantly in both groups (P=0.001). Follistatin to myostatin ratio increased significantly in both groups (P=0.001). Although body fat percentage decreased in both groups, it did not differ significantly between the two groups (P=0.28). Moreover, anaerobic power increased significantly in both groups (P=0.001), but this increase was more profound in the BFRT group (P=0.001). Conclusion: Based on our findings, blood flow restriction can be applied as remarkable approach to boost body adaptation responses to resistance training.

In most cases, pharmacologic strategies to treat genetic muscle disorders and certain acquired disorders, such as sporadic inclusion body myositis, have produced modest clinical benefits. In these conditions, inhibition of the myostatin pathway represents an alternative strategy to improve functional outcomes. Preclinical data that support this approach clearly demonstrate the potential for blocking the myostatin pathway. Follistatin has emerged as a powerful antagonist of myostatin that can increase muscle mass and strength. Follistatin was first isolated from the ovary and is known to suppress follicle-stimulating hormone. This raises concerns for potential adverse effects on the hypothalamic–pituitary–gonadal axis and possible reproductive capabilities. In this review we demonstrate a strategy to bypass off-target effects using an alternatively spliced cDNA of follistatin (FS344) delivered by adeno-associated virus (AAV) to muscle. The transgene product is a peptide of 315 amino acids that is secreted from the muscle and circulates in the serum, thus avoiding cell-surface binding sites. Using this approach our translational studies show increased muscle size and strength in species ranging from mice to monkeys. Adverse effects are avoided, and no organ system pathology or change in reproductive capabilities has been seen. These findings provide the impetus to move toward gene therapy clinical trials with delivery of AAV-FS344 to increase size and function of muscle in patients with neuromuscular disease. Muscle Nerve 39: 283–296, 2009

Transplanted Spemann’s organizer induces dorsal embryonic cell fates such as the nervous system and somites, but in normal development, elimination of individual organizer signals (such as the bone morphogenetic protein [BMP] antagonists) has surprisingly modest effects on these tissues. Thus, the role of BMP antagonists may be limited to fine tuning the size of the dorsal domain. However, at least five BMP antagonists are specifically expressed in the organizer, and all can mimic aspects of organizer function, suggesting overlapping functions. Here, we deplete the function of three BMP antagonists, chordin, noggin, and follistatin, in Xenopus tropicalis. We demonstrate that this results in catastrophic failure of dorsal development and expansion of ventral and posterior fates. We conclude that BMP antagonists are required for formation of the neural plate and dorsal mesoderm. In addition, our results show that neural specification requires the continuous activity of BMP antagonists from blastula through gastrula stages.

Bone quality is an important determinant of osteoporosis, and proper osteoblast differentiation plays an important role in the control and maintenance of bone quality. We investigated the impact of activin signaling on human osteoblast differentiation, extracellular matrix formation, and mineralization. Activins belong to the transforming growth factor-beta superfamily and activin A treatment strongly inhibited mineralization in osteoblast cultures, whereas the activin antagonist follistatin increased mineralization. Osteoblasts produced activin A and follistatin in a differentiation-dependent manner, leading to autocrine regulation of extracellular matrix formation and mineralization. In addition, mineralization in a vascular smooth muscle cell-based model for pathological calcification was inhibited. Comparative activin A and follistatin gene expression profiling showed that activin signaling changes the expression of a specific range of extracellular matrix proteins prior to the ...

To explore the potential roles of inhibin, activin, and follistatin in human oocyte development by quantifying their intrafollicular biosynthesis. Prospective, nonrandomized study. An IVF unit and academic research laboratory. Thirty one patients undergoing IVF. Human menopausal gonadotropins or human FSH (or both) were administered. Single-follicle aspirates (n = 110) were collected for analysis. Concentrations of dimeric, total and pro-alphaC inhibin forms; activin A; follistatin; estradiol; and progesterone were measured in follicular fluids. Granulosa-cell mRNA was analyzed for alpha, beta A, and beta B inhibin and activin subunits; follistatin; activin receptors; and beta-actin. Hormone concentrations and mRNA levels were correlated with oocytes or embryos from the same follicles. Levels of progesterone and follistatin were significantly greater in follicles containing MI or MII oocytes than in those containing GV oocytes. Inhibin alpha-subunit mRNA levels were significantly higher in follicles containing maturing oocytes, the highest-quality oocytes, and oocytes that were subsequently fertilized. In contrast, inhibin alpha-subunit mRNA levels were significantly lower in follicles from which higher-quality embryos were obtained. Inhibin alpha-subunit biosynthesis is associated with normal oocyte and follicle maturation, but excessive alpha-inhibin is associated with poor embryo quality. None of the hormones analyzed were associated with oocyte or embryo quality.

Current treatments for advanced stage, hormone-resistant prostate cancer are largely ineffective, leading to high patient mortality and morbidity. To fulfill this unmet medical need, we used global gene expression profiling to identify new potential antibody-drug ...

Current genetic data are equivocal as to whether goat domestication occurred multiple times or was a singular process. We generated genomic data from 83 ancient goats (51 with genome-wide coverage) from Paleolithic to Medieval contexts throughout the Near East. Our findings demonstrate that multiple divergent ancient wild goat sources were domesticated in a dispersed process that resulted in genetically and geographically distinct Neolithic goat populations, echoing contemporaneous human divergence across the region. These early goat populations contributed differently to modern goats in Asia, Africa, and Europe. We also detect early selection for pigmentation, stature, reproduction, milking, and response to dietary change, providing 8000-year-old evidence for human agency in molding genome variation within a partner species.

Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area compared to cardiac myocytes. The conditional ablation of Fstl1 in S100a4-expressing fibroblast lineage cells (Fstl1-cfKO mice) led to a reduction in injury-induced Fstl1 expression and increased mortality due to cardiac rupture during the acute phase. Cardiac rupture was associated with a diminished number of myofibroblasts and decreased expression of extracellular matrix proteins. The infarcts of Fstl1-cfKO mice displayed weaker birefringence, indicative of thin and loosely packed collagen. Mechanistically, the migratory and proliferative capabilities of cardiac fibroblasts were attenuated by endogenous Fstl1 ablation. The activation of cardiac fibroblasts by Fstl1 was m...

Do seminal plasma transforming growth factor-β (TGFB) cytokines vary within individuals over time, and does this relate to sperm parameters, age or prior abstinence? Activin A and follistatin, and to a lesser extent TGFB1, TGFB2 and TGFB3, vary within individuals over time, in association with duration of abstinence. Seminal plasma TGFB cytokines can influence sperm function and reproductive success through interactions with the female reproductive tract after coitus. Over time, individual sperm parameters fluctuate considerably. Whether seminal fluid TGFB cytokines vary similarly, and the determinants of any variance, is unknown. Between two and seven semen samples were collected from each of 14 fertile donors at 6-10 week intervals over the course of 12 months, then seminal plasma cytokines and sperm parameters were measured. The concentrations and total amounts per ejaculate of TGFB1, TGFB2, TGFB3, activin A and follistatin were determined using commercial assays. Sperm parameter...

The runt domain transcription factors are key regulators of developmental processes in bilaterians, involved both in cell proliferation and differentiation, and their disruption usually leads to disease. Three runt domain genes have been described in each vertebrate genome (the RUNX gene family), but only one in other chordates. Therefore, the common ancestor of vertebrates has been thought to have had a single runt domain gene. Analysis of the genome draft of the fugu pufferfish (Takifugu rubripes) reveals the existence of a fourth runt domain gene, FrRUNT, in addition to the orthologs of human RUNX1, RUNX2 and RUNX3. The tiny FrRUNT packs six exons and two putative promoters in just 3 kb of genomic sequence. The first exon is located within an intron of FrSUPT3H, the ortholog of human SUPT3H, and the first exon of FrSUPT3H resides within the first intron of FrRUNT. The two gene structures are therefore &quot;interlocked&quot;. In the human genome, SUPT3H is instead interlocked wit...

For neural crest cells to engage in migration, it is necessary that epithelial premigratory crest cells convert into mesenchyme. The mechanisms that trigger cell delamination from the dorsal neural tube remain poorly understood. We find that, in 15- to 40-somite-stage avian embryos, BMP4 mRNA is homogeneously distributed along the longitudinal extent of the dorsal neural tube, whereas its specific inhibitor noggin exists in a gradient of expression that decreases caudorostrally. This rostralward reduction in signal intensity coincides with the onset of emigration of neural crest cells. Hence, we hypothesized that an interplay between Noggin and BMP4 in the dorsal tube generates graded concentrations of the latter that in turn triggers the delamination of neural crest progenitors. Consistent with this suggestion, disruption of the gradient by grafting Noggin-producing cells dorsal to the neural tube at levels opposite the segmental plate or newly formed somites, inhibited emigration ...

Activin-A may exert pro- or anti-tumorigenic activities depending on cellular context. However, little is known about its role, or the other mature activin proteins, in colorectal carcinoma (CRC). This study measured the expression of activin βA- & βB-subunits, activin type IIA & IIB receptors, smads 2/3/4/6/7 and follistatin in CRC induced by azoxymethane (AOM) in rats. The results were compared with controls and disseminated according to the characteristics of histopathological lesions. Eighty male Wistar rats were allocated into 20 controls and the remaining were equally divided between short &#39;S-AOM&#39; (15 weeks) and long &#39;L-AOM&#39; (35 weeks) groups following injecting AOM for 2 weeks. Subsequent to gross and histopathological examinations and digital image analysis, the expression of all molecules was measured by immunohistochemistry and quantitative RT-PCR. Activin-A, activin-B, activin-AB and follistatin were measured by ELISA in serum and colon tissue homogenates....