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Felice Petraglia – One of the best experts on this subject based on the ideXlab platform.

  • PlAcentAl And mAternAl serum Activin A in spontAneous And induced lAbor in lAte-term pregnAncy
    Journal of Endocrinological Investigation, 2018
    Co-Authors: L. Funghi, Filiberto Maria Severi, M. Torricelli, R. Novembri, S. Vannuccini, G. Cevenini, M. Di Tommaso, Felice Petraglia

    Abstract:

    Purpose Feto-plAcentAl unit represents An importAnt source of Activin A, A member of trAnsforming growth fActors-β involved in the mechAnisms of lAbor. No evidences Are AvAilAble on Activin A in pregnAncies beyond 41 weeks of gestAtion, where induction of lAbor is often required. The present study Aimed to evAluAte Activin A mAternAl serum levels And plAcentAl mRNA expression in term And lAte-term pregnAncy, with spontAneous or induced lAbor, And its possible role to predict the response to lAbor induction. Methods MAternAl serum sAmples And plAcentAl specimens were collected from women with singleton pregnAncy Admitted for either term spontAneous lAbor ( n  = 23) or induction of lAbor for lAte-term pregnAncy ( n  = 41), to evAluAte Activin A serum levels And plAcentAl mRNA expression. UnivAriAte And multivAriAte AnAlyses on Activin A serum levels, mAternAl clinicAl pArAmeters, And cervicAl length were conducted in women undergoing induction of lAbor. Results MAternAl serum Activin A levels And plAcentAl Activin A mRNA expression in lAte-term pregnAncies were significAntly higher thAn At term. LAte-term pregnAncies who did not respond to induction of lAbor showed significAntly lower levels of Activin A compAred to responders. The combinAtion of serum Activin A And cervicAl length Achieved A sensitivity of 100% And A specificity of 93.55% for the prediction of successful induction. Conclusion LAte-term pregnAncy is chArActerized by hyperexpression of plAcentAl Activin A And increAsed mAternAl Activin A secretion. By combining mAternAl serum Activin A levels with cervicAl length, A good predictive model for the response to induction of lAbor wAs elAborAted.

  • EndometriAl Expression And Secretion of Activin A, But Not FollistAtin, IncreAse in the Secretory PhAse of the MenstruAl Cycle
    , 2016
    Co-Authors: Felice Petraglia

    Abstract:

    OBJECTIVE: Activin A is A growth fActor expressed by humAn endometrium, And its biologic effects Are counterActed byfollistAtin. We evAluAte whether Activin A AndfollistAtin mRNA And peptide expression As well As protein secretion from humAn endometrium chAnge throughout the menstruAl cycle. METHODS: In 25 heAlthy fertile pAtients, uterine wAshing fluid wAs retrieved by hydrosonogrAphy. In A subgroup (n = 13), endometriAl tissue sAmples were collected by hysteroscopy during the proliferAtive (n = 6) or secretory (n = 7) phAse of the menstruAl cycle. Activin And follistAtin mRNA And peptide expression were evAluAted by reverse trAnscriptAse-polymerAse chAin reAction (RT-PCR) And by immuno-histochemistry (IHC), respectively. Activin A AndfollistAtin levels were AssAyed in uterine wAshing fluids by specific enzyme-linked immunosorbent AssAys And evAluAted According to the endometriAl thickness And menstruAl cycle dAys. RESULTS: Both Activin A AndfollistAtin mRNAs were expressed by humAn endometrium, And their peptides immunolocAlized both in proliferAtive And secretory endometriAl epitheliAl And stromAl cells. A significAnt increAse in immunoreActive Activin PA but not infollistAtin wAs observed in glAndulAr epithelium during the secretory phAse. Activin A but notfollistAtin wAs significAntly (P < 0001) higher in the wAshing fluids collected during the secretory thAn proliferAtive phAse of the menstruAl cycle. In Addition, A significAnt correlAtion wAsfound between Activin A, but notfollistAtin, And menstruAl cycle dAys (P <.0001) or endometriAl thickness (P <.0001). CONCLUSION: Both Activin A AndfollistAtin mRNAs Are expressed by humAn endometrium; however, Activin A but notfollistAtin peptide expression And secretion were increAsed in the secretory phAse of the menstruAl cycle, suggesting An importAnt role in humAn endometrium. (J Soc Gynecol Investig 2003; 10

  • UlipristAl AcetAte ModulAtes the Expression And Functions of Activin A in LeiomyomA Cells
    Reproductive Sciences, 2014
    Co-Authors: Pasquapina Ciarmela, Patrizia Carrarelli, Md Soriful Islam, Milijana Janjusevic, Errico Zupi, Claudia Tosti, Mario Castellucci, Felice Petraglia

    Abstract:

    Uterine leiomyomA is the most common benign gynecologicAl tumor in women of reproductive Age And represents the single most common indicAtion for hysterectomy. A development of new treAtments is necessAry for A medicAl mAnAgement, And in this direction, severAl hormonAl drugs Are under investigAtion. UlipristAl AcetAte (UPA; A selective progesterone receptor modulAtor) is considered As one of the most promising becAuse progesterone hAs A criticAl role in development And growth of uterine leiomyomA. The effect of steroids is pArtly mediAted by growth fActors like Activin A which increAses extrAcellulAr mAtrix expression contributing to the growth of leiomyomA. The present study Aimed to test whether UPA Acts on leiomyomA cells Affecting expression And functions of Activin A system. Cultured myometriAl And leiomyomA cells were treAted with UPA, And messenger RNA (mRNA) expression levels of Activin A (inhibin βA [INHBA] subunits), its binding proteins (follistAtin [FST] And FST-relAted gene), And its receptors (Activin receptor-like kinAse 4 [ALK4], Activin receptor type [ActR] II, And ActRIIB) were evAluAted. The effect of UPA on Activin A modulAtion of fibronectin And vAsculAr endotheliAl growth fActor A (VEGF-A) mRNA expression in cultured myometriAl And leiomyomA cells wAs Also studied. UlipristAl AcetAte decreAsed INHBA, FST, ActRIIB, And Alk4 mRNA expressions in leiomyomA cultured cells. In Addition, UPA wAs Able to block the Activin A-induced increAse in fibronectin or VEGF-A mRNA expression in myometriAl And in leiomyomA cultured cells. The present dAtA show thAt UPA inhibits Activin A expression And functions in leiomyomA cells, And this mAy represent A possible mechAnism of Action of the drug on uterine leiomyomA.

Pasquale Florio – One of the best experts on this subject based on the ideXlab platform.

  • single serum Activin A testing to predict ectopic pregnAncy
    The Journal of Clinical Endocrinology and Metabolism, 2007
    Co-Authors: Pasquale Florio, Stefano Luisi, Filiberto Maria Severi, Caterina Bocchi, Massimo Mazzini, S Danero, Michela Torricelli, Felice Petraglia

    Abstract:

    Context: Ectopic pregnAncy (EP) is An importAnt cAuse of mAternAl deAths in eArly pregnAncy becAuse most fAtAl cAses result from delAyed diAgnosis And inAppropriAte investigAtion. Objective: We evAluAted whether the meAsurement of Activin A mAy be useful in the diAgnosis of EP in women with unknown pregnAncy locAtion. Design: The study wAs designed As An open observAtionAl study. Setting: The study wAs set in A tertiAry referrAl center for obstetric cAre. PAtients: PAtients were women with unknown pregnAncy locAtion (n 536) who hAd complAints of bleeding, pAin, or crAmping. Interventions: Interventions included clinicAl exAminAtion; trAnsvAginAl ultrAsound scAn; humAn chorionic gonAdotropin (hCG), progesterone, And Activin A meAsurements; lApAroscopy; uterine curettAge; And histologicAl exAminAtion. MAinOutcomeMeAsures:MAinoutcomemeAsureswerepregnAncy outcomes And evAluAtion of sensitivity, specificity, And predictive vAlues of hCG, progesterone, And Activin A As diAgnostic tests for the detection of EP. Results: PregnAncy outcomes included 155 (28.9%) viAble intrAuterine pregnAncies (IUP), 305 (56.9%) first-trimester spontAneous Abortion (SAB), And 76 (14.2%) EP. SAB hAd the lowest (P 0.0001) hCG And progesterone concentrAtions, significAntly lower thAn EP (P 0.001) And IUP (P 0.001). In EP, levels were significAntly (P 0.001)lowerthAninIUP.OnthecontrAry,ActivinAlevelswerelowest (P 0.0001) in EP, significAntly lower thAn in SAB (P 0.001) And IUP (P 0.001). IUP hAd significAntly (P 0.001) lower Activin A levels thAn SAB. When evAluAted by the receiver operAting curve AnAlysis, Activin A At the cutoff of 0.37 ng/ml combined A sensitivity And A specificity of 100 And 99.6%, respectively, for prediction of EP. When Activin A concentrAtions were below the cutoff, the positive predictive vAlue for EP wAs 97.43%, And 0% for concentrAtions higher thAn 0.37 ng/ml. Conclusions: Activin A meAsurement mAy identify pAtients At risk of EP with A high sensibility And specificity. (J Clin Endocrinol MetAb 92: 1748–1753, 2007)

  • Activin A In BrAin Injury
    Advances in clinical chemistry, 2007
    Co-Authors: Pasquale Florio, Stefano Luisi, Diego Gazzolo, Felice Petraglia

    Abstract:

    1. AbstrAct Activin A is A growth fActor composed of two βA subunits belonging to the trAnsforming growth fActor β (TGF‐β) superfAmily of dimeric proteins. The biologicAl Activity of Activin A is mediAted by two different types of receptors, the type I (ARI And ARIB) And the type II receptors (ARII And ARIIB), And by two Activin‐binding proteins, follistAtin And follistAtin‐relAted gene. These fActors bind to Activin A And thereby inhibit its biologicAl effects. Activin A, its receptors, And binding proteins Are widely distributed throughout the brAin. Studies employing models of Acute brAin injury strongly implicAte enhAnced Activin A expression As A common response to Acute neuronAl dAmAge of vArious origins. Hypoxic/ischemic injury, mechAnicAl irritAtion, And chemicAl dAmAge of brAin evoke A strong upregulAtion of Activin A. Subsequent experimentAl studies hAve shown thAt Activin A hAs A beneficiAl role to neuronAl recovery And thAt, by ActivAting different pAthwAys, Activin A hAs robust neuroprotective Activities. BecAuse Activin A induction occurs eArly After brAin injury, its meAsurement mAy provide A potentiAl biochemicAl index of the presence, locAtion, And extent of brAin injury. This ApproAch mAy Also fAcilitAte the diAgnosis of subclinicAl lesions At stAges when monitoring procedures Are unAble to detect brAin lesion And furthermore estAblish A prognosis.

  • effect of Activin A on tumor necrosis fActor α intercellulAr Adhesion molecule 1 pAthwAy in endometriAl stromAl cells
    European Journal of Obstetrics & Gynecology and Reproductive Biology, 2005
    Co-Authors: Silvia Mangioni, Pasquale Florio, Felice Petraglia, Paola Vigano, Orietta Borghi, M Vignali, Anna Maria Di Blasio

    Abstract:

    AbstrAct Objective[s] Activin A And inhibin A Are growth fActors expressed by humAn endometrium involved in the control of endometriAl functions. In the present study we investigAted the effects of Activin A And inhibin A in modulAting the tumor necrosis fActor (TNF)-α/intercellulAr Adhesion molecule (ICAM)-1 system in cultured humAn endometriAl stromAl cells. Study design EndometriAl sAmples were obtAined from 34 reproductive Age women undergoing lApAroscopy for benign ovAriAn cysts or infertility. EndometriAl stromAl cells were cultured And soluble ICAM-1 And TNF-α were meAsured in cell-free supernAtAnts following treAtment with or without Activin A or inhibin A. Cell surfAce ICAM-1 wAs AssAyed by flow cytometry by stAining endometriAl cells with specific monoclonAl Antibodies. Results Activin A And inhibin A did not influence either the expression of cell surfAce ICAM-1 or soluble ICAM-1 shedding by cultured endometriAl cells. On the other hAnd, TNF-α secretion significAntly increAsed in presence of Activin A but not of inhibin A. Conclusions Since TNF-α modulAtes severAl endometriAl processes such As menstruAtion, proliferAtion, Apoptosis, implAntAtion And deciduAlizAtion, An effect of Activin A in the physiologicAl control of endometrium is further supported by the present dAtA.

Stefano Luisi – One of the best experts on this subject based on the ideXlab platform.

  • single serum Activin A testing to predict ectopic pregnAncy
    The Journal of Clinical Endocrinology and Metabolism, 2007
    Co-Authors: Pasquale Florio, Stefano Luisi, Filiberto Maria Severi, Caterina Bocchi, Massimo Mazzini, S Danero, Michela Torricelli, Felice Petraglia

    Abstract:

    Context: Ectopic pregnAncy (EP) is An importAnt cAuse of mAternAl deAths in eArly pregnAncy becAuse most fAtAl cAses result from delAyed diAgnosis And inAppropriAte investigAtion. Objective: We evAluAted whether the meAsurement of Activin A mAy be useful in the diAgnosis of EP in women with unknown pregnAncy locAtion. Design: The study wAs designed As An open observAtionAl study. Setting: The study wAs set in A tertiAry referrAl center for obstetric cAre. PAtients: PAtients were women with unknown pregnAncy locAtion (n 536) who hAd complAints of bleeding, pAin, or crAmping. Interventions: Interventions included clinicAl exAminAtion; trAnsvAginAl ultrAsound scAn; humAn chorionic gonAdotropin (hCG), progesterone, And Activin A meAsurements; lApAroscopy; uterine curettAge; And histologicAl exAminAtion. MAinOutcomeMeAsures:MAinoutcomemeAsureswerepregnAncy outcomes And evAluAtion of sensitivity, specificity, And predictive vAlues of hCG, progesterone, And Activin A As diAgnostic tests for the detection of EP. Results: PregnAncy outcomes included 155 (28.9%) viAble intrAuterine pregnAncies (IUP), 305 (56.9%) first-trimester spontAneous Abortion (SAB), And 76 (14.2%) EP. SAB hAd the lowest (P 0.0001) hCG And progesterone concentrAtions, significAntly lower thAn EP (P 0.001) And IUP (P 0.001). In EP, levels were significAntly (P 0.001)lowerthAninIUP.OnthecontrAry,ActivinAlevelswerelowest (P 0.0001) in EP, significAntly lower thAn in SAB (P 0.001) And IUP (P 0.001). IUP hAd significAntly (P 0.001) lower Activin A levels thAn SAB. When evAluAted by the receiver operAting curve AnAlysis, Activin A At the cutoff of 0.37 ng/ml combined A sensitivity And A specificity of 100 And 99.6%, respectively, for prediction of EP. When Activin A concentrAtions were below the cutoff, the positive predictive vAlue for EP wAs 97.43%, And 0% for concentrAtions higher thAn 0.37 ng/ml. Conclusions: Activin A meAsurement mAy identify pAtients At risk of EP with A high sensibility And specificity. (J Clin Endocrinol MetAb 92: 1748–1753, 2007)

  • Activin A And FollistAtin in MenstruAl Blood: Low ConcentrAtions in Women With DysfunctionAl Uterine Bleeding
    Reproductive Sciences, 2007
    Co-Authors: Fernando M. Reis, Stefano Luisi, Lívia L. Nascimento, Anastasia Tsigkou, Márcia C. Ferreira, Felice Petraglia

    Abstract:

    Activin A And follistAtin Are growth fActors produced by severAl orgAns, comprising the endometrium, where they modulAte cell And tissue differentiAtion. In this study, the Authors tested whether Activin A And follistAtin Are meAsurAble in menstruAl blood And whether their concentrAtions chAnge in women with dysfunctionAl uterine bleeding (DUB). The Authors evAluAted heAlthy women with regulAr menstruAl cycles (n = 15) And women with DUB (n = 12). Activin A And follistAtin were meAsured in both menstruAl And peripherAl blood sAmples using highly sensitive enzyme immunoAssAys, whereAs their respective mRNAs were quAntified by reAl-time polymerAse chAin reAction in endometriAl sAmples collected during the perimenstruAl period. Activin A concentrAtions were 4-fold higher in menstruAl thAn in peripherAl serum of heAlthy women (meAn ± SE, 4.24 ± 0.18 vs 1.00 ± 0.15 ng/mL, P < .001) And were significAntly lower in women with DUB compAred to heAlthy subjects ( P < .001). FollistAtin concentrAtion wAs 8-fold higher in menstruAl thAn in peripherAl serum of heAlthy women (3.94 ± 0.49 vs 0.49 ± 0.04 ng/mL, P < .001) And wAs significAntly lower in the menstruAl serum of women with DUB compAred to controls ( P < .001). There wAs no correlAtion between menstruAl And peripherAl serum concentrAtions of both proteins. The endometriAl expression of Activin A And follistAtin mRNA wAs lower in women with DUB compAred to controls ( P < .05). Both Activin A And follistAtin Are meAsurAble in high concentrAtions in humAn menstruAl blood And Are relAtively lower in women with DUB. The quAntitAtive Assessment of Activin A And follistAtin in menstruAl serum might be A putAtive clinicAl mArker of endometriAl function.

  • Activin A In BrAin Injury
    Advances in clinical chemistry, 2007
    Co-Authors: Pasquale Florio, Stefano Luisi, Diego Gazzolo, Felice Petraglia

    Abstract:

    1. AbstrAct Activin A is A growth fActor composed of two βA subunits belonging to the trAnsforming growth fActor β (TGF‐β) superfAmily of dimeric proteins. The biologicAl Activity of Activin A is mediAted by two different types of receptors, the type I (ARI And ARIB) And the type II receptors (ARII And ARIIB), And by two Activin‐binding proteins, follistAtin And follistAtin‐relAted gene. These fActors bind to Activin A And thereby inhibit its biologicAl effects. Activin A, its receptors, And binding proteins Are widely distributed throughout the brAin. Studies employing models of Acute brAin injury strongly implicAte enhAnced Activin A expression As A common response to Acute neuronAl dAmAge of vArious origins. Hypoxic/ischemic injury, mechAnicAl irritAtion, And chemicAl dAmAge of brAin evoke A strong upregulAtion of Activin A. Subsequent experimentAl studies hAve shown thAt Activin A hAs A beneficiAl role to neuronAl recovery And thAt, by ActivAting different pAthwAys, Activin A hAs robust neuroprotective Activities. BecAuse Activin A induction occurs eArly After brAin injury, its meAsurement mAy provide A potentiAl biochemicAl index of the presence, locAtion, And extent of brAin injury. This ApproAch mAy Also fAcilitAte the diAgnosis of subclinicAl lesions At stAges when monitoring procedures Are unAble to detect brAin lesion And furthermore estAblish A prognosis.