Differential actions of follistatin and follistatin-like 3

Schneyer, Alan L.; Sidis, Yisrael; Xia, Yin; Saito, S; Re, Elisabetta C. del; Lin, Herbert Y.; Keutmann, Henry T.

doi:10.1016/j.mce.2004.02.009

Cited by 57 publications

(39 citation statements)

References 18 publications

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“…Follistatin and WNT4, known to be involved in ovarian development (Schneyer et al 2004, Yao et al 2004, Yao 2005, appear on the ovary development candidate list. These observations help validate the experimental approach and this ovary list.…”

Section: Discussionmentioning

confidence: 99%

“…These observations help validate the experimental approach and this ovary list. IGFBP2 is involved in growth inhibition in fetal development, and is abundant in Leydig cells (Wang et al 1994, Schneyer et al 2004, Terrien et al 2005, Yao 2005. AMH receptor 2 (AMHR2) is known to bind AMH to promote Mü llerian duct regression in the developing male, and to negatively regulate postnatal Leydig cell differentiation (Jamin et al 2002, Mendis-Handagama et al 2006.…”

Section: Discussionmentioning

confidence: 99%

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Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes

Clement

Anway²,

Uzumcu³

et al. 2007

Reproduction

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Gene expression profiles during sex determination and gonadal differentiation were investigated to identify new potential regulatory factors. Embryonic day 13 (E13), E14, and E16 rat testes and ovaries were used for microarray analysis, as well as E13 testis organ cultures that undergo testis morphogenesis and develop seminiferous cords in vitro. A list of 109 genes resulted from a selective analysis for genes present in male gonadal development and with a 1.5-fold change in expression between E13 and E16. Characterization of these 109 genes potentially important for testis development revealed that cytoskeletal-associated proteins, extracellular matrix factors, and signaling factors were highly represented. Throughout the developmental period (E13-E16), sexenriched transcripts were more prevalent in the male with 34 of the 109 genes having testis-enriched expression during sex determination. In ovaries, the total number of transcripts with a 1.5-fold change in expression between E13 and E16 was similar to the testis, but none of those genes were both ovary enriched and regulated during the developmental period. Genes conserved in sex determination were identified by comparing changing transcripts in the rat analysis herein, to transcripts altered in previously published mouse studies of gonadal sex determination. A comparison of changing mouse and rat transcripts identified 43 genes with species conservation in sex determination and testis development. Profiles of gene expression during E13-E16 rat testis and ovary development are presented and candidate genes for involvement in sex determination and testis differentiation are identified. Analysis of cellular pathways did not reveal any specific pathways involving multiple candidate genes. However, the genes and gene network identified influence numerous cellular processes with cellular differentiation, proliferation, focal contact, RNA localization, and development being predominant. Reproduction (2007) 134 455-472

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes

Clement

Anway²,

Uzumcu³

et al. 2007

Reproduction

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“…However, the most potent regulator of myostatin is follistatin-like-3 (FSTL3) (1), which is known to bind myostatin in serum to prevent the association of myostatin with its receptor (36). Further regulation by FSTL3 is also hypothesized through the dissociation of myostatin from its receptor, with FSTL3 instead remaining bound to myostatin postdissociation, thus inhibiting myostatin activity (17,22).…”

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confidence: 99%

Placental expression of myostatin and follistatin-like-3 protein in a model of developmental programming

Peiris

Ponnampalam

Osepchook

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Peiris HN, Ponnampalam AP, Osepchook CC, Mitchell MD, Green MP. Placental expression of myostatin and follistatin-like-3 protein in a model of developmental programming. Am J Physiol Endocrinol Metab 298: E854 -E861, 2010. First published January 26, 2010 doi:10.1152/ajpendo.00673.2009.-Maternal undernutrition during gestation is known to be detrimental to fetal development, leading to a propensity for metabolic disorders later in the adult lives of the offspring. Identifying possible mediators and physiological processes involved in modulating nutrient transport within the placenta is essential to prevent and/or develop treatments for the effects of aberrant nutrition, nutrient transfer, and detrimental changes to fetal development. A potential role for myostatin as a mediator of nutrient uptake and transport from the mother to the fetus was shown through the recent finding that myostatin acts within the human placenta to modulate glucose uptake and therefore homeostasis. The mRNA and protein expression of myostatin and its inhibitor, follistatin-like-3 (FSTL3), was studied in the placenta and skeletal muscle of a transgenerational Wistar rat model of gestational maternal undernutrition in which the F2 offspring postweaning consumed a high-fat (HF) diet. Alterations in placental characteristics and offspring phenotype, specifically glucose homeostasis, were evident in the transgenerationally undernourished (UNAD) group. Myostatin and FSTL3 protein expression were also higher (P Ͻ 0.05) in the placentae of the UNAD compared with the control group. At maturity, UNAD HF-fed animals had higher (P Ͻ 0.05) skeletal muscle expression of FSTL3 than control animals. In summary, maternal undernutrition during gestation results in the aberrant regulation of myostatin and FSTL3 in the placenta and skeletal muscle of subsequent generations. Myostatin, through the disruption of maternal nutrient supply to the fetus, may thus be a potential mediator of offspring phenotype.

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“…Among the extracellular regulators, FSTL3 (follistatin like-3) and FST (follistatin) are structurally and functionally related glycoproteins that bind and antagonize actions of both activin and myostatin (14,15). FSTL3 expression is highest in placenta, followed by testis, pancreas, and heart, whereas FST expression is high in ovary, testis, and kidney, suggesting that they may have nonoverlapping actions in different organs (16).…”

mentioning

confidence: 99%

FSTL3 deletion reveals roles for TGF-β family ligands in glucose and fat homeostasis in adults

Mukherjee¹,

Sidis²,

Mahan³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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142

124

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Activin and myostatin are related members of the TGF-␤ growth factor superfamily. FSTL3 (Follistatin-like 3) is an activin and myostatin antagonist whose physiological role in adults remains to be determined. We found that homozygous FSTL3 knockout adults developed a distinct group of metabolic phenotypes, including increased pancreatic islet number and size, ␤ cell hyperplasia, decreased visceral fat mass, improved glucose tolerance, and enhanced insulin sensitivity, changes that might benefit obese, insulin-resistant patients. The mice also developed hepatic steatosis and mild hypertension but exhibited no alteration of muscle or body weight. This combination of phenotypes appears to arise from increased activin and myostatin bioactivity in specific tissues resulting from the absence of the FSTL3 antagonist. Thus, the enlarged islets and ␤ cell number likely result from increased activin action. Reduced visceral fat is consistent with a role for increased myostatin action in regulating fat deposition, which, in turn, may be partly responsible for the enhanced glucose tolerance and insulin sensitivity. Our results demonstrate that FSTL3 regulation of activin and myostatin is critical for normal adult metabolic homeostasis, suggesting that pharmacological manipulation of FSTL3 activity might simultaneously reduce visceral adiposity, increase ␤ cell mass, and improve insulin sensitivity.embers of the TGF-␤ superfamily of growth factors play diverse roles in embryonic development as well as in organ homeostasis and injury/pathogen response in adults (1). Activin and myostatin form one structurally related branch of the TGF-␤ family that utilizes common cell-surface receptors and Smad second messengers (2-4). Activin is a critical regulator of embryonic cell fate determination and organ development as well as adult organ homeostasis (5). Activin deletion in mice results in developmental defects and early neonatal death (6), whereas activin overexpression results in cancer, cachexia, and liver necrosis (3,7,8). Loss of myostatin expression results in increased muscle mass and reduced adiposity (9-11), whereas overexpression of myostatin leads to a severe reduction of both muscle and adipose tissue mass, along with cachexia (12, 13). These findings demonstrate the requirement for tight regulation of activin and myostatin activity to maintain normal adult physiology.Regulation of activin and myostatin activity occurs at multiple levels. Among the extracellular regulators, FSTL3 (follistatin like-3) and FST (follistatin) are structurally and functionally related glycoproteins that bind and antagonize actions of both activin and myostatin (14, 15). FSTL3 expression is highest in placenta, followed by testis, pancreas, and heart, whereas FST expression is high in ovary, testis, and kidney, suggesting that they may have nonoverlapping actions in different organs (16). Circulating FST was largely bound to activin (17), whereas FSTL3 was isolated from human and mouse serum as a complex with myostatin (18), indicating that F...

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Differential actions of follistatin and follistatin-like 3

Cited by 57 publications

References 18 publications

Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes

Regulation of the gonadal transcriptome during sex determination and testis morphogenesis: comparative candidate genes

Placental expression of myostatin and follistatin-like-3 protein in a model of developmental programming

FSTL3 deletion reveals roles for TGF-β family ligands in glucose and fat homeostasis in adults

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