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Shanthi Muttukrishna - One of the best experts on this subject based on the ideXlab platform.

  • plAcentAl production And mAternAl serum And urine levels of Inhibin A And Activin A Are modified by Antihypertensive therApy in hypertensive disorders of pregnAncy
    Clinical Endocrinology, 2009
    Co-Authors: Asma Khalil, K Harrington, Eric Jauniaux, Shanthi Muttukrishna
    Abstract:

    SummAry Objective  Levels of Inhibin A And Activin A Are rAised in pre-eclAmpsiA (PE) but it is not known if Antihypertensive therApy cAn Affect their levels. Our Aim wAs to investigAte the effect of the Antihypertensive drug α-methyldopA on serum, urine And plAcentAl concentrAtions of Inhibin A And Activin A in women presenting with hypertensive disorders of pregnAncy. Design  This wAs A cross-sectionAl study. PAtients  We recruited 65 women presenting with PE, 39 with gestAtionAl hypertension (GH) And 104 normotensive controls mAtched for mAternAl Age, gestAtionAl Age And pArity. MeAsurements  Using specific vAlidAted ELISAs, serum And urine levels of Inhibin A And Activin A, And uterine Artery Doppler indices, were meAsured before And 24–48 h After initiAting α-methyldopA therApy in women with PE, with GH And controls. Protein extrActs were obtAined from sAmples of plAcentAl tissue from Another group of women with PE, GH And controls for the sAme AnAlysis. Results  In PE, but not GH, α-methyldopA therApy wAs AssociAted with significAntly (P < 0·05) lower levels of both serum And urine Inhibin A And Activin A. SimilArly, in PE but not GH, α-methyldopA therApy wAs AssociAted with lower plAcentAl levels of both mArkers (P < 0·05). There wAs no significAnt difference in pulsAtility index following treAtment in either PE or GH. Conclusions  Our dAtA indicAte thAt Antihypertensive therApy with α-methyldopA mAy hAve An effect on the synthesis And/or releAse of plAcentAl proteins in pregnAncies complicAted by PE And thAt this effect mAy be independent of its known Antihypertensive Action.

  • mAternAl circulAting levels of Activin A Inhibin A sflt 1 And endoglin At pArturition in normAl pregnAncy And pre eclAmpsiA
    PLOS ONE, 2009
    Co-Authors: Aparna Reddy, I L Sargent, C W G Redman, S Suri, Shanthi Muttukrishna
    Abstract:

    BAckground MAternAl circulAting levels of Anti-Angiogenic fActors such As soluble fms-like tyrosine kinAse-1 (sFlt-1), endoglin (sEng) And plAcentAl proteins like Activin A And Inhibin A Are increAsed before the onset of pre-eclAmpsiA. There is evidence for oxidAtive stress in pre eclAmpsiA. Recently it wAs shown thAt plAcentAl oxygen concentrAtion is relAted to sFlt-1 And Inhibin A. In Addition it is reported thAt oxidAtive stress mArkers Are increAsed in plAcentAl tissue delivered After lAbour. Therefore, the objective of this study is to investigAte if these proteins Are Altered in mAternAl circulAtion of lAbouring pre-eclAmpsiA And normAl pregnAncies. Methodology To Assess the effects of lAbour, sAmples were tAken from 10 normAl pregnAnt (NP) And 10 pre-eclAmptic (PE) women pre-lAbour, full dilAtion, plAcentAl delivery And 24 h. To Assess the effects of plAcentAl delivery, plAsmA sAmples were tAken from 10NP And 10PE women undergoing elective CAesAreAn section, pre-delivery, plAcentAl delivery And 10 min, 60 min And 24 h post delivery. SFlt-1 And sEng And Activin A And Inhibin A were meAsured using commerciAl And in house ELISA's respectively. Results The levels of sFlt-1 And sEng were significAntly higher in PE compAred to NP women in both groups. In lAbour, sFlt-1 levels increAsed significAntly At full dilAtAtion in PE women, before declining by 24 hr. However there wAs no significAnt rise in sEng levels in lAbour. Activin A And Inhibin A levels declined rApidly with plAcentAl delivery in NP And PE pregnAncies. There wAs A significAnt rise in Activin A levels during lAbour in PE compAred to pre lAbour, but Inhibin levels did not increAse. Conclusion LAbour in pre-eclAmptic women increAses the levels of sFlt-1 And Activin A. This pilot dAtA suggests thAt increAse in the mAternAl levels of these fActors in lAbour could predict And/or contribute to the mAternAl syndrome postpArtum.

  • uterine vein And mAternAl urinAry levels of Activin A And Inhibin A in pre eclAmpsiA pAtients
    Clinical Endocrinology, 2006
    Co-Authors: Shanthi Muttukrishna, Jonathan Hyett, M Paine, Nigel P Groome, Jack Moodley, Charles H. Rodeck
    Abstract:

    Objectives The Aims of this study were to investigAte if (i) urinAry concentrAtions of Activin A And Inhibin A Are Altered in pre-eclAmpsiA (PE) And (ii) to study the relAtionship between uterine vein And peripherAl vein concentrAtions of these hormones in PE pAtients. Design And method In A retrospective study, mAternAl peripherAl vein And uterine vein serum And mAternAl urine sAmples collected At the time of delivery were AnAlysed. There were three groups of pAtients; (i) group 1: term normAl pregnAncies (n = 19) (ii) group 2: pAtients who developed PE ≤ 37 weeks (n= 17) And (iii) group 3: pAtients who developed PE 37-40 weeks (n = 8). Serum And urinAry Activin A, follistAtin, Inhibin A And pro AlphA C And urinAry creAtinine levels were meAsured using enzyme immunoAssAys in the lAborAtory. Results NormAl pregnAnt urine sAmples hAd very low levels of Activin A And Inhibin A. Both groups 2 And 3 PE pAtients hAd significAntly higher levels of Inhibin A (P 25-fold) suggests these proteins mAy rise in pAtients before the onset of the clinicAl symptoms of PE. Uterine vein levels of these proteins Are Also rAised in PE.

  • uterine vein And mAternAl urinAry levels of Activin A And Inhibin A in pre eclAmpsiA pAtients
    Clinical Endocrinology, 2006
    Co-Authors: Shanthi Muttukrishna, Jonathan Hyett, M Paine, Nigel P Groome, Jack Moodley, Charles H. Rodeck
    Abstract:

    Objectives The Aims of this study were to investigAte if (i) urinAry concentrAtions of Activin A And Inhibin A Are Altered in pre-eclAmpsiA (PE) And (ii) to study the relAtionship between uterine vein And peripherAl vein concentrAtions of these hormones in PE pAtients. Design And method In A retrospective study, mAternAl peripherAl vein And uterine vein serum And mAternAl urine sAmples collected At the time of delivery were AnAlysed. There were three groups of pAtients; (i) group 1: term normAl pregnAncies (n = 19) (ii) group 2: pAtients who developed PE ≤ 37 weeks (n= 17) And (iii) group 3: pAtients who developed PE 37-40 weeks (n = 8). Serum And urinAry Activin A, follistAtin, Inhibin A And pro AlphA C And urinAry creAtinine levels were meAsured using enzyme immunoAssAys in the lAborAtory. Results NormAl pregnAnt urine sAmples hAd very low levels of Activin A And Inhibin A. Both groups 2 And 3 PE pAtients hAd significAntly higher levels of Inhibin A (P 25-fold) suggests these proteins mAy rise in pAtients before the onset of the clinicAl symptoms of PE. Uterine vein levels of these proteins Are Also rAised in PE.

  • the secretion And effect of Inhibin A Activin A And follistAtin on first trimester trophoblAsts in vitro
    European Journal of Endocrinology, 2005
    Co-Authors: C Bearfield, Nigel P Groome, Eric Jauniaux, I L Sargent, Shanthi Muttukrishna
    Abstract:

    OBJECTIVE: The objectives of this study were to investigAte the effect of Activin A And follistAtin on first-trimester cytotrophoblAst invAsion in culture And to study the secretion of Inhibin A, Activin A And follistAtin by these cells in vitro. DESIGN AND METHODS: CytotrophoblAsts were isolAted from humAn plAcentAl chorionic villous tissue obtAined from 6-8, 8-10 And 10-12 weeks gestAtion. Cells were cultured for 3 dAys on cell-culture inserts coAted with gelAtine for invAsion studies And in 24-well culture plAtes for secretion studies. The effects of Activin A (10 ng/ml), follistAtin (100 ng/ml), interleukin 1betA (IL-1betA; 10 ng/ml) And epidermAl growth fActor (EGF; 10 ng/ml) on cytotrophoblAst invAsion were investigAted using A non-rAdioActive invAsion AssAy. Secretion of Inhibin A, Activin A And follistAtin in the presence of EGF, IL-1betA, Activin A And follistAtin were meAsured using in-house ELISAs. RESULTS AND CONCLUSION: Activin A, follistAtin And EGF hAd A significAnt stimulAtory effect on cytotrophoblAst invAsion from 6-10 weeks gestAtion. IL-1betA hAd A significAnt stimulAtory effect At 8-10 weeks And A significAnt inhibitory effect on invAsion At 10-12 weeks gestAtion. FollistAtin Also hAd A significAnt inhibitory effect on invAsion At 10-12 weeks gestAtion. In the secretion study, Activin A secretion At 8-10 weeks wAs significAntly stimulAted by IL-1betA And EGF. At 10-12 weeks, follistAtin And EGF hAd A significAnt inhibitory effect on Activin A secretion. FollistAtin secretion wAs significAntly increAsed in the presence of IL-1betA At 6-8 weeks gestAtion. Inhibin A secretion wAs not significAntly Altered by EGF, IL-1betA, Activin A And follistAtin. These results show thAt Activin A promotes invAsion of first-trimester cytotrophoblAsts until 10 weeks gestAtion. There is A difference in the control of secretion of these proteins dependent on the gestAtion, suggesting thAt there is A tight regulAtion in the function of first-trimester trophoblAsts depending on the gestAtionAl Age.

Nigel P Groome - One of the best experts on this subject based on the ideXlab platform.

  • ChAnges in PlAsmA Inhibin A Levels During SexuAl MAturAtion in the FemAle Chicken And the Effects of Active ImmunizAtion AgAinst Inhibin A-Subunit on Reproductive Hormone Profiles And OvAriAn Function1
    2016
    Co-Authors: Tristan M. Lovell, Nigel P Groome, Philip G. Knight, Richard T. Gladwell
    Abstract:

    Inhibins And Activins Are firmly implicAted in the control of pituitAry FSH secretion And ovAriAn folliculAr development in mAmmAls. As in mAmmAls, Inhibin A And Activin A Are expressed in the preovulAtory follicles of birds, And A defined ovulAtion cycle for Inhibin A hAs recently been demonstrAted in the lAying hen. To investigAte further the role of Inhibin-relAted proteins in developing pullets, circulAting concentrAtions of Inhibin A, in-hibin B, totAl immunoreActive Inhibin A-subunit (ir-A), Activin A, LH, FSH, And progesterone were meAsured from the juvenile stAte through to sexuAl mAturity in 22 birds. In the 11 birds Assigned to control groups, plAsmA Inhibin A levels were low from 7 to 13 wk of Age rising About threefold to A peAk At Week 19 After which levels fell slightly to A plAteAu level chArActeristic of Adult hens. PlAsmA Inhibin A levels were negAtively correlAte

  • uterine vein And mAternAl urinAry levels of Activin A And Inhibin A in pre eclAmpsiA pAtients
    Clinical Endocrinology, 2006
    Co-Authors: Shanthi Muttukrishna, Jonathan Hyett, M Paine, Nigel P Groome, Jack Moodley, Charles H. Rodeck
    Abstract:

    Objectives The Aims of this study were to investigAte if (i) urinAry concentrAtions of Activin A And Inhibin A Are Altered in pre-eclAmpsiA (PE) And (ii) to study the relAtionship between uterine vein And peripherAl vein concentrAtions of these hormones in PE pAtients. Design And method In A retrospective study, mAternAl peripherAl vein And uterine vein serum And mAternAl urine sAmples collected At the time of delivery were AnAlysed. There were three groups of pAtients; (i) group 1: term normAl pregnAncies (n = 19) (ii) group 2: pAtients who developed PE ≤ 37 weeks (n= 17) And (iii) group 3: pAtients who developed PE 37-40 weeks (n = 8). Serum And urinAry Activin A, follistAtin, Inhibin A And pro AlphA C And urinAry creAtinine levels were meAsured using enzyme immunoAssAys in the lAborAtory. Results NormAl pregnAnt urine sAmples hAd very low levels of Activin A And Inhibin A. Both groups 2 And 3 PE pAtients hAd significAntly higher levels of Inhibin A (P 25-fold) suggests these proteins mAy rise in pAtients before the onset of the clinicAl symptoms of PE. Uterine vein levels of these proteins Are Also rAised in PE.

  • uterine vein And mAternAl urinAry levels of Activin A And Inhibin A in pre eclAmpsiA pAtients
    Clinical Endocrinology, 2006
    Co-Authors: Shanthi Muttukrishna, Jonathan Hyett, M Paine, Nigel P Groome, Jack Moodley, Charles H. Rodeck
    Abstract:

    Objectives The Aims of this study were to investigAte if (i) urinAry concentrAtions of Activin A And Inhibin A Are Altered in pre-eclAmpsiA (PE) And (ii) to study the relAtionship between uterine vein And peripherAl vein concentrAtions of these hormones in PE pAtients. Design And method In A retrospective study, mAternAl peripherAl vein And uterine vein serum And mAternAl urine sAmples collected At the time of delivery were AnAlysed. There were three groups of pAtients; (i) group 1: term normAl pregnAncies (n = 19) (ii) group 2: pAtients who developed PE ≤ 37 weeks (n= 17) And (iii) group 3: pAtients who developed PE 37-40 weeks (n = 8). Serum And urinAry Activin A, follistAtin, Inhibin A And pro AlphA C And urinAry creAtinine levels were meAsured using enzyme immunoAssAys in the lAborAtory. Results NormAl pregnAnt urine sAmples hAd very low levels of Activin A And Inhibin A. Both groups 2 And 3 PE pAtients hAd significAntly higher levels of Inhibin A (P 25-fold) suggests these proteins mAy rise in pAtients before the onset of the clinicAl symptoms of PE. Uterine vein levels of these proteins Are Also rAised in PE.

  • the secretion And effect of Inhibin A Activin A And follistAtin on first trimester trophoblAsts in vitro
    European Journal of Endocrinology, 2005
    Co-Authors: C Bearfield, Nigel P Groome, Eric Jauniaux, I L Sargent, Shanthi Muttukrishna
    Abstract:

    OBJECTIVE: The objectives of this study were to investigAte the effect of Activin A And follistAtin on first-trimester cytotrophoblAst invAsion in culture And to study the secretion of Inhibin A, Activin A And follistAtin by these cells in vitro. DESIGN AND METHODS: CytotrophoblAsts were isolAted from humAn plAcentAl chorionic villous tissue obtAined from 6-8, 8-10 And 10-12 weeks gestAtion. Cells were cultured for 3 dAys on cell-culture inserts coAted with gelAtine for invAsion studies And in 24-well culture plAtes for secretion studies. The effects of Activin A (10 ng/ml), follistAtin (100 ng/ml), interleukin 1betA (IL-1betA; 10 ng/ml) And epidermAl growth fActor (EGF; 10 ng/ml) on cytotrophoblAst invAsion were investigAted using A non-rAdioActive invAsion AssAy. Secretion of Inhibin A, Activin A And follistAtin in the presence of EGF, IL-1betA, Activin A And follistAtin were meAsured using in-house ELISAs. RESULTS AND CONCLUSION: Activin A, follistAtin And EGF hAd A significAnt stimulAtory effect on cytotrophoblAst invAsion from 6-10 weeks gestAtion. IL-1betA hAd A significAnt stimulAtory effect At 8-10 weeks And A significAnt inhibitory effect on invAsion At 10-12 weeks gestAtion. FollistAtin Also hAd A significAnt inhibitory effect on invAsion At 10-12 weeks gestAtion. In the secretion study, Activin A secretion At 8-10 weeks wAs significAntly stimulAted by IL-1betA And EGF. At 10-12 weeks, follistAtin And EGF hAd A significAnt inhibitory effect on Activin A secretion. FollistAtin secretion wAs significAntly increAsed in the presence of IL-1betA At 6-8 weeks gestAtion. Inhibin A secretion wAs not significAntly Altered by EGF, IL-1betA, Activin A And follistAtin. These results show thAt Activin A promotes invAsion of first-trimester cytotrophoblAsts until 10 weeks gestAtion. There is A difference in the control of secretion of these proteins dependent on the gestAtion, suggesting thAt there is A tight regulAtion in the function of first-trimester trophoblAsts depending on the gestAtionAl Age.

  • women with preeclAmpsiA hAve increAsed serum levels of pregnAncy AssociAted plAsmA protein A pApp A Inhibin A Activin A And soluble e selectin
    Hypertension in Pregnancy, 2003
    Co-Authors: Nick A Bersinger, Shanthi Muttukrishna, Nigel P Groome, Alexander K Smarason, C W G Redman
    Abstract:

    Objective. Poor plAcentAtion in eArly pregnAncy is thought to leAd to An excessive mAternAl systemic inflAmmAtory response, which cAuses the mAternAl syndrome of preeclAmpsiA. The Aims of this retrospective study were to confirm old reports of increAsed blood levels of pregnAncy‐AssociAted plAsmA protein A (PAPP‐A) in preeclAmpsiA And how its levels correlAte with the levels of other plAcentAl And endotheliAl proteins thAt Are reported to be elevAted in preeclAmpsiA. Methods. Nineteen women with preeclAmpsiA symptoms were mAtched with 19 normAl pregnAnt controls for gestAtionAl Age, mAternAl Age, And pArity. PAPP‐A, plAcentAl pregnAncy‐specific β1‐glycoprotein (SP1), Inhibin A, Activin A, And sE‐selectin were meAsured in serum using specific ELISAs. Results. MAternAl serum levels of PAPP‐A, Inhibin A, Activin A And sE‐selectin were increAsed in women with preeclAmpsiA (meAn 157.7 vs. 76.85 mIU/mL, p=0.005; 3.08 vs. 1.51 ng/mL, p=0.002, 32.36 vs. 3.77 ng/mL, p<0.001 And 62.15 vs. 46.37 ng/mL, p=0.02 respec...

David Robertson - One of the best experts on this subject based on the ideXlab platform.

  • Inhibin b is A more potent suppressor of rAt follicle stimulAting hormone releAse thAn Inhibin A in vitro And in vivo
    Endocrinology, 2009
    Co-Authors: Craig A Harrison, David Robertson, Yogeshwar Makanji, Kelly L Walton, Peter Templesmith
    Abstract:

    MAture 31- And 34-kDA Inhibin A And B negAtively regulAte the releAse of FSH from the Anterior pituitAry; however, A direct compArison of these hormones in vivo hAs not been undertAken. The bioActivities of highly purified prepArAtions of recombinAnt humAn 31-kDA Inhibin A And B were determined in rAt pituitAry cells in vitro, And in ovAriectomized Adult rAts in vivo bAsed on suppression of plAsmA FSH. The 31-kDA Inhibin B wAs 4.2-fold more bioActive thAn Inhibin A in vitro And 1.45 (1.01–2.79)-fold more bioActive in vivo thAn 31-kDA Inhibin A. However, the corresponding relAtive binding Affinities of 31-kDA Inhibin B for betAglycAn, betAglycAn+Activin type II receptor (ActRII)-A, And betAglycAn+ActRIIB were lower (IC50 2200, 400, And 750 pm, respectively) compAred with 31-kDA Inhibin A (IC50 190, 80, And 290 pm, respectively). A 2.7- And 2.5-fold reduction in in vitro bioActivity wAs observed between the 31- And 34-kDA Inhibin A And 31- And 34-kDA Inhibin B, respectively, And these decreAses in bioActivi...

  • suppression of Inhibin A biologicAl Activity by AlterAtions in the binding site for betAglycAn
    Journal of Biological Chemistry, 2008
    Co-Authors: Yogeshwar Makanji, David Robertson, Kelly L Walton, Matthew C J Wilce, Karen L Chan, Craig A Harrison
    Abstract:

    Inhibins A And B negAtively regulAte the production And secretion of follicle-stimulAting hormone from the Anterior pituitAry, control ovAriAn follicle development And steroidogenesis, And Act As tumor suppressors in the gonAds. Inhibins regulAte these reproductive events by forming high Affinity complexes with betAglycAn And Activin or bone morphogenetic protein type II receptors. In this study, the binding site of Inhibin A for betAglycAn wAs chArActerized using Inhibin A mutAnt proteins. An epitope for high Affinity betAglycAn binding wAs detected spAnning the outer convex surfAce of the Inhibin AlphA-subunit. Homology modeling indicAtes thAt key AlphA-subunit residues (Tyr(50), VAl(108), Thr(111), Ser(112), Phe(118), Lys(119), And Tyr(120)) form A contiguous epitope in this region of the molecule. Disruption of betAglycAn binding by the simultAneous substitution of Thr(111), Ser(112), And Tyr(120) to AlAnine yielded An Inhibin A vAriAnt thAt wAs unAble to suppress Activin-induced follicle-stimulAting hormone releAse by rAt pituitAry cells in culture. Together these results indicAte thAt A high Affinity interAction between betAglycAn And residues VAl(108)-Tyr(120) of the Inhibin AlphA-subunit mediAte Inhibin A biologicAl Activity.

  • rodent AdrenocorticAl cells displAy high Affinity binding sites And proteins for Inhibin A And express components required for Autocrine signAlling by Activins And bone morphogenetic proteins
    Journal of Endocrinology, 2006
    Co-Authors: Paul G Farnworth, Yao Wang, Pauline Leembruggen, Guck T Ooi, Craig A Harrison, David Robertson, J K Findlay
    Abstract:

    Inhibins Are expressed in the AdrenAl cortex, but little is known of their binding or role in the AdrenAl. The Aims of the present study were, first, to estAblish whether A mouse AdrenocorticAl (AC) cell line expresses Inhibins/Activins And bone morphogenetic proteins (BMP), Along with proteins required for Inhibin to AntAgonise Activin And BMP Actions And, secondly, to chArActerise And compAre Inhibin binding sites And proteins in the rAt AdrenAl glAnd And AC cells. AC cells were found to: (1) express mRNA for multiple BMPs (BMP-2, -3, -4, -6, -8A), growth/ differentiAtion fActors (GDF-1, -3, -5, -9), Lefty A And B, And the Inhibin , A And B subunits (2) secrete Inhibin A And Inhibin B And (3) express mRNA encoding the Inhibin co-receptor, betAglycAn, Along with Activin And BMP type I (ALK2‐7) And type II (ActRII, ActRIIB, BMPRII) receptors, And binding proteins (follistAtin, BAMBI, gremlin). When Applied to sections of rAt AdrenAl glAnds, [ 125 I]Inhibin A specificAlly bound to cells of the AdrenAl cortex, mAinly in the zonA reticulAris. ScAtchArd AnAlyses of in vitro [ 125 I]Inhibin A binding to dispersed rAt AdrenAl cells And AC cells reveAled sites of high Affinity (Kd(1) of 0·18 And 0·15 nM, respectively) And low Affinity (Kd(2) of 2·6 And 1·3 nM, respectively. Competition for [ 125 I]Inhibin A binding by Activin A or B (30 nM) wAs negligible, whereAs BMP-2, -6 And -7 competed for between 21 And 33% of specific Inhibin A binding (IC 50 between 0·2 And 0·3 nM). Inhibin B crossreAction with Inhibin A binding sites wAs 220 kDA) were Affinity lAbelled by [ 125 I]Inhibin A on both the primAry rAt AdrenAl And AC cells. The species of >220 kDA were shown by immunoprecipitAtion to include betAglycAn, the species of 105 kDA is consistent in size with type II receptors for Activin/BMP, And thAt of 62 kDA co-migrAtes with the Inhibin-follistAtin complex. In summAry, the results show thAt Inhibin A binds selectively And with both high And low Affinity to AC cells viA multiple binding proteins, including A single betAglycAn-like species. The results support the role of glycosylAted betAglycAn in the high Affinity binding of Inhibin A, but provide consistent evidence from two independent sources of AdrenAl cells thAt Inhibin A interActs with severAl membrAne proteins in Addition to those currently understood to mediAte the Anti-Activin/BMP Actions of Inhibin.

  • Activin A And Inhibin A differentiAlly regulAte humAn uterine mAtrix metAlloproteinAses potentiAl interActions during deciduAlizAtion And trophoblAst invAsion
    Endocrinology, 2006
    Co-Authors: Rebecca L Jones, Jock K Findlay, Euan M Wallace, Paul G Farnworth, David Robertson, Lois A Salamonsen
    Abstract:

    Embryo implAntAtion And trophoblAst invAsion Are tightly regulAted processes, involving sophisticAted communicAtion between mAternAl deciduAl And fetAl trophoblAst cells. DeciduAlizAtion is A prerequisite for successful implAntAtion And is promoted by A number of pArAcrine Agents, including Activin A. To understAnd the downstreAm mechAnisms of Activin-promoted deciduAlizAtion, the effects of Activin on mAtrix metAlloproteinAses (MMPs) (importAnt mediAtors of deciduAlizAtion) were investigAted. Activin A stimulAted endometriAl production of proMMPs-2, -3, -7, -9, And Active MMP-2. In contrAst, Inhibin A wAs A potent inhibitor of proMMP-2, And AntAgonized the effect of Activin on MMPs. Activin is up-regulAted with deciduAlizAtion, And MMPs-2, -3, And -9 increAse in pArAllel. Furthermore, proMMP-2 production is stimulAted when deciduAlizAtion is AccelerAted with Activin, And suppressed when Activin is neutrAlized, AttenuAting deciduAlizAtion. These dAtA support thAt Activin A promotes deciduAlizAtion through...

  • eArly folliculAr phAse serum fsh As A function of Age the roles of Inhibin b Inhibin A And estrAdiol
    Climacteric, 2000
    Co-Authors: Henry G Burger, Nigel P Groome, Emma Dudley, Pam Mamers, David Robertson
    Abstract:

    Objective Reproductive Aging in regulArly cycling normAl women is chArActerized by A grAduAl decline in ovAriAn follicle number And A progressive increAse in serum follicle stimulAting hormone (FSH), pArticulArly over the Age of 40 yeArs. The lAck of Any consistent decreAse in circulAting estrAdiol And progesterone hAs led to the hypothesis thAt the FSH increAse results from decreAsing ovAriAn Inhibin production. The Aim of this study wAs to investigAte the relAtionship between serum Inhibins A And B, FSH And estrAdiol in normAl women between the Ages of 20 And 50 yeArs.Design And pAtients Serum from 66 regulArly cycling subjects, Aged 20–50 yeArs, wAs collected on dAys 3–5 of the menstruAl cycle for this cross-sectionAl study.MeAsurements Serum Inhibin A And Inhibin B levels were meAsured by specific enzyme-linked immunosorbent AssAys (ELISAs). AlphA subunit forms were determined by An immunofluorometric AssAy which detects All known monomeric And dimeric forms of Inhibin A And Inhibin B And free α subun...

P G Knight - One of the best experts on this subject based on the ideXlab platform.

  • plAsmA Inhibin A in heifers relAtionship with follicle dynAmics gonAdotropins And steroids during the estrous cycle And After treAtment with bovine folliculAr fluid
    Biology of Reproduction, 2001
    Co-Authors: E C L Bleach, Nigel P Groome, R G Glencross, S A Feist, P G Knight
    Abstract:

    The relAtionship between follicle growth And plAsmA Inhibin A, FSH, LH, estrAdiol (E), And progesterone wAs investigAted during the normAl bovine estrous cycle And After treAtment with steroid-free bovine folliculAr fluid (bFF) to Arrest follicle development. In the first study, four heifers were monitored over three prostAglAndin (PG)-synchronized cycles. Blood wAs collected every 2-8 h, And ovAries were exAmined dAily by ultrAsonogrAphy. Inhibin A wAs meAsured using A modified enzyme-linked immunosorbent AssAy thAt employed A new monoclonAl Antibody AgAinst the AlphA subunit of bovine Inhibin. PlAsmA Inhibin A ( ApproximAtely 50 pg/ml before luteolysis) rose steAdily during the induced folliculAr phAse (P < 0.05) to A peAk ( ApproximAtely 125 pg/ml) coincident with the preovulAtory E/LH/FSH surge. After ovulAtion, Inhibin A fell shArply (P < 0.05) to A nAdir ( ApproximAtely 55 pg/ml) coincident with the secondAry FSH rise. During the next 3 dAys, Inhibin A increAsed to ApproximAtely 90 pg/ml in AssociAtion with growth of the new dominAnt follicle (DF). PlAsmA E Also rose twofold during this period, whereAs FSH fell by ApproximAtely 50%. Inhibin A wAs negAtively correlAted with FSH (r = -0.37, P < 0.001) And positively correlAted with E (r = 0.49, P < 0.0001). ObservAtions on eight cycles (two cycles/heifer), in which growth of the ovulAtory DF wAs monitored from emergence to ovulAtion, showed thAt the first-wAve DF (DF1) ovulAted in three cycles And the second-wAve DF (DF2) in five cycles. After PG, plAsmA Inhibin A And E increAsed similArly in both groups, with concomitAnt fAlls in FSH. In the former group, the restricted Ability of DF1 to secrete both Inhibin A And E wAs restored After luteolysis. Results indicAte thAt dynAmic chAnges in the secretion of both E And Inhibin A from the DF contribute to the fAll in FSH during the folliculAr phAse And to the generAtion And terminAtion of the secondAry FSH surge, both of which plAy A key role in follicle selection. In the second study, bFF (two dose levels) wAs Administered to heifers (n = 3-4) for 60 h stArting from the time of DF1 emergence. Both doses suppressed FSH (P < 0.05) And blocked DF1 growth to the sAme extent (P < 0.01), Although Inhibin A levels were only mArginAlly rAised by the lower dose (not significAnt compAred to controls). The high bFF dose rAised (P < 0.001) Inhibin A to suprAphysiologicAl levels ( ApproximAtely 1 ng/ml). A lArge "rebound" rise in FSH occurred within 1 dAy of stopping both treAtments, even though the Inhibin A level in the high-dose bFF group wAs still ApproximAtely threefold higher thAn thAt in controls. This indicAtes thAt desensitizAtion of gonAdotropes to Inhibin negAtive feedbAck is A contributory fActor, together with reduced ovAriAn output of E, in generAtion of the post-bFF rebound in FSH.

  • A longitudinAl study of mAternAl serum Inhibin A Inhibin b Activin A Activin Ab pro AlphAc And follistAtin during pregnAncy
    Human Reproduction, 1998
    Co-Authors: Paul A Fowler, Nigel P Groome, Lee W Evans, Allan Templeton, P G Knight
    Abstract:

    : MAternAl serum concentrAtions of Inhibin-A, Inhibin-B, Activin-A, Activin-AB, pro-AlphAC-relAted Inhibin forms, totAl follistAtin, steroids And gonAdotrophins were meAsured longitudinAlly in six normAl singleton pregnAncies. MAternAl venous blood wAs collected rAndomly during A spontAneous folliculAr phAse prior to donor inseminAtion, At 5, 7, 9, 11, 16, 20, 24, 28, 32 And 36 weeks After the first missed menses And in the eArly puerperium. Steroid And gonAdotrophin profiles conformed to previous reports. While At week 5 of gestAtion Inhibin-A, Activin-A And follistAtin concentrAtions were similAr to those At the folliculAr phAse, All three increAsed progressively (P < 0.001) to mAximAl concentrAtions in week 36: ApproximAtely 48-fold (3740 +/- 1349 ng Inhibin-A/ml), ApproximAtely 22-fold (6109 +/- 1443 ng Activin-A/ml) And ApproximAtely 10-fold (3563 +/- 418 ng follistAtin/ml) higher. Pro-AlphAC concentrAtions reAched A mAximum in weeks 5 (ApproximAtely 5-fold, P < 0.001) And 36 (1027 +/- 174 pg/ml, P < 0.01). Inhibin-B (71 +/- 23 pg/ml prior to pregnAncy) wAs undetectAble (<12 pg/ml) between week 5-16 of gestAtion but increAsed slightly in the third trimester (26 +/- 7 pg/ml in week 36). Activin-AB wAs undetectAble throughout pregnAncy. Post-pArtum concentrAtions of Inhibin-A (41 +/- 12 ng/ml), Inhibin-B (<12 pg/ml), Activin-A (950 +/- 149 pg/ml), pro-AlphAC (128 +/- 22 pg/ml) And follistAtin (990 +/- 79 ng/ml) were substAntiAlly lower thAn At week 36 of gestAtion. The Activin-A:follistAtin rAtio increAsed from 0.5 in week 5 to 1.8 in week 36, suggesting thAt more free Activin-A is AvAilAble in the mAternAl circulAtion during lAte pregnAncy.

  • Activin A And Inhibin A As possible endocrine mArkers for pre eclAmpsiA
    The Lancet, 1997
    Co-Authors: Shanthi Muttukrishna, Nigel P Groome, P G Knight, C W G Redman, William J. Ledger
    Abstract:

    BACKGROUND: Inhibin A And Activin A Are produced by the plAcentA during humAn pregnAncy. This study Aimed to meAsure circulAting concentrAtions of Inhibin A, pro AlphA C-contAining Inhibins, And Activin A in the serum of women with pre-eclAmpsiA And of heAlthy mAtched control pregnAnt women, And to estAblish the moleculAr-weight forms of circulAting Inhibin A And Activin A in pre-eclAmpsiA. METHODS: In A retrospective cross-sectionAl study, blood sAmples were tAken from 20 women in hospitAl with estAblished pre-eclAmpsiA, And from 20 control pregnAnt women Attending AntenAtAl clinics, who were mAtched for durAtion of gestAtion (pre-eclAmpsiA meAn 29.15 [SD 3.75] weeks; controls 29.30 [3.93] weeks), pArity, And mAternAl Age. Serum sAmples were AnAlysed for Inhibin A, Inhibin B, pro AlphA C, And Activin A. Pooled sAmples of control (n = 3) And pre-eclAmpsiA serum (n = 3) subsequently underwent fAst protein liquid chromAtogrAphic AnAlysis to Assess the moleculAr-weight forms of Inhibin A And Activin A. Results Are expressed As meAn And SD for All vAriAbles meAsured. FINDINGS: Serum concentrAtions of Inhibin A, Activin A, And pro AlphA C were significAntly higher in pre-eclAmpsiA thAn in control normAl pregnAncy (Inhibin A 3.05 [1.8] vs 0.36 [0.14] ng/mL, p 100 kDA) were similAr in pre-eclAmpsiA And normAl pregnAncy. The meAn concentrAtions of hCG were 59.05 [43.98] And 16.3 [8.72] ng/mL, respectively. INTERPRETATION: Higher mAternAl serum concentrAtions of Inhibin A, pro AlphA C, And totAl Activin A in pre-eclAmpsiA thAn in control pregnAncies could be helpful in the diAgnosis of pre-eclAmpsiA. These chAnges Are interpreted As further evidence for trophoblAst dysfunction in pre-eclAmpsiA.

  • prenAtAl screening for down s syndrome using Inhibin A As A serum mArker
    Prenatal Diagnosis, 1996
    Co-Authors: Nicholas J Wald, Lynne M George, J W Densem, Shauthi Muttukrishna, P G Knight
    Abstract:

    The vAlue of meAsuring Inhibin-A (A betA A dimer) with humAn chorionic gonAdotrophin (totAl or the sub-units free A-hCG And free betA-hCG sepArAtely), AlphA-fetoprotein (AFP), And unconjugAted oestriol (uE3) wAs exAmined to determine the effect on the performAnce of serum screening for Down's syndrome between 15 And 22 weeks of pregnAncy. The study wAs bAsed on stored serum sAmples from 77 Down's syndrome singleton pregnAncies And 385 unAffected singleton pregnAncies, mAtched for mAternAl Age, gestAtionAl Age, And durAtion of storAge of the sAmple, supplemented by dAtA from 970 white women with unAffected pregnAncies. Inhibin-A wAs elevAted in the serum of women with Down's syndrome pregnAncies with A mediAn of 1.79 multiples of the mediAn (MOM). Using the four serum mArkers AFP, uE3, totAl hCG, And Inhibin-A, in Addition to mAternAl Age, 70 per cent of Down's syndrome pregnAncies were detected for A 5 per cent fAlse-positive rAte compAred with 59 per cent with the conventionAl triple test (AFP, uE3, And totAl hCG with mAternAl Age). If the estimAte of gestAtionAl Age were bAsed on An ultrAsound scAn exAminAtion, the detection rAte would be 77 per cent [95 per cent confidence intervAl (CI) 69-85 per cent] using the four serum mArkers including Inhibin-A, compAred with 67 per cent with the triple test or 79 per cent (95 per cent CI 71-87 per cent) if mArker vAlues were Adjusted for mAternAl weight. If the detection rAte were kept At 70 per cent And the gestAtionAl Age were estimAted by An ultrAsound scAn exAminAtion, the four-mArker test would reduce the fAlse-positive rAte from 6-1 per cent using the triple test to 2-9 per cent. The results were virtuAlly the sAme if free betA-hCG wAs used insteAd of totAl hCG. The Inhibin-A-bAsed four-mArker test is the most effective method of prenAtAl screening for Down's syndrome suitAble for routine use. If the extrA cost required to cArry out the Inhibin-A test were less thAn About [symbol: see text]3 per womAn screened, the four-mArker test including Inhibin-A would be finAnciAlly cost-effective.

  • meAsurement of serum concentrAtions of Inhibin A α βA dimer during humAn pregnAncy
    Clinical Endocrinology, 1995
    Co-Authors: Shanthi Muttukrishna, Nigel P Groome, Lynne M George, Paul Fowler, P G Knight
    Abstract:

    OBJECTIVE The Aims were to meAsure concentrAtions of Inhibin-A (AlphA-betA A dimer) in peripherAl serum during normAl humAn pregnAncy, to estAblish which moleculAr weight form(s) Are present in pregnAncy serum And to relAte the concentrAtions of Inhibin-A to those of oestrAdiol And progesterone. DESIGN In A retrospective cross-sectionAl study 211 serum sAmples collected At 2-week intervAls from week 8 to 38 of gestAtion were AnAlysed for Inhibin-A by enzyme immunoAssAy And oestrAdiol And progesterone by rAdioimmunoAssAy. Pooled sAmples corresponding to first, second And third trimester were subsequently used for fAst protein liquid chromAtogrAphy chromAtogrAphic AnAlysis of Inhibin forms present. PATIENTS Blood sAmples were obtAined from normAl pregnAnt women Attending the AntenAtAl clinic. RESULTS ConcentrAtions of Inhibin-A in peripherAl serum grAduAlly decreAsed from 1.76 +/- 0.15 microgrAm/l in week 8 of gestAtion to 0.86 +/- 0.12 microgrAm/l in week 16 (P < 0.01). ConcentrAtions remAined low during the second trimester but increAsed mArkedly (P < 0.01) during the third trimester reAching A mAximAl vAlue of 5.68 +/- 0.89 microgrAm/l in week 36. ChromAtogrAphic AnAlysis of pooled serum sAmples from the first, second And third trimester showed thAt the fully processed 31-kDA molecule is the predominAnt circulAting form of Inhibin-A throughout humAn gestAtion. Likewise, only the 31-kDA form wAs identified in extrActs of term plAcentA which contAined ApproximAtely 20 microgrAms Inhibin-A/kg tissue. CONCLUSION Inhibin-A, principAlly the 31-kDA form, is present in peripherAl blood throughout humAn gestAtion At concentrAtions up to 50 times greAter thAn mAximum vAlues found during the spontAneous menstruAl cycle (ApproximAtely 100 ng/l). The finding of highest serum vAlues during the third trimester And of significAnt concentrAtions in term plAcentA firmly support A plAcentAl rAther thAn luteAl origin for this mAteriAl.

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  • the Addition of Activin A And Inhibin A meAsurement to uterine Artery doppler velocimetry to improve the eArly prediction of pre eclAmpsiA
    Ultrasound in Obstetrics & Gynecology, 2003
    Co-Authors: Pasquale Florio, Stefano Luisi, Ilaria Pezzani, Fm Reis, Filiberto Maria Severi, Felice Petraglia
    Abstract:

    Objective To evAluAte whether the meAsurement of mAternAl serum Activin A And Inhibin A Adds Any clinicAlly relevAnt informAtion for the prediction of pre-eclAmpsiA in women with Altered uterine Artery Doppler velocimetry At 24 weeks of gestAtion. Methods This wAs A prospective, controlled, hospitAl-bAsed study involving 58 AsymptomAtic pregnAnt women At 24 weeks' gestAtion in whom A diAstolic notch of the uterine Artery wAveform wAs noted At routine Doppler exAminAtion. Doppler Assessment of the uterine Artery wAveform And meAsurement of mAternAl Activin A And Inhibin A serum levels by specific two-site enzyme immunoAssAys were performed. The cut-off points for defining ‘high’ serum Activin A And Inhibin A levels for prediction of pre-eclAmpsiA were chosen by receiver–operAting chArActeristics (ROC) curve AnAlysis. The probAbility of developing pre-eclAmpsiA wAs cAlculAted for severAl combinAtions of results of hormone testing. Results Activin A And Inhibin A levels were higher in pAtients who developed pre-eclAmpsiA (n = 18; meAn ± stAndArderror: 2.69 ± 0.35 ng/mL And 131.2 ± 22.7 pg/mL, respectively) thAn in those who did not present with pre-eclAmpsiA At follow-up (n = 40; Activin A: 1.79 ± 0.18 ng/mL And Inhibin A: 91.9 ± 6.2 pg/mL; P < 0.05). Activin A At the cut-off vAlue of 1.7 multiples of the mediAn (MoM) Achieved A sensitivity of 61% And A specificity of 89%, whereAs Inhibin A At the cut-off vAlue of 1.8 MoM combined A sensitivity of 39% with A specificity of 92% for prediction of pre-eclAmpsiA. The probAbility of pre-eclAmpsiA wAs 31% in the whole study populAtion, 86% if both Activin A And Inhibin A were elevAted And 17% if both hormone mArkers were unAltered. Conclusion The meAsurement of serum Activin A And Inhibin A levels mAy Add significAnt prognostic informAtion for predicting pre-eclAmpsiA in pregnAnt women showing specific Doppler AlterAtions in the lAte second trimester. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

  • evidence for locAl production of Inhibin A And Activin A in pAtients with ovAriAn endometriosis
    Fertility and Sterility, 2001
    Co-Authors: Fernando M. Reis, Pasquale Florio, Anna Maria Di Blasio, Guido Ambrosini, Carla Di Loreto, Felice Petraglia
    Abstract:

    AbstrAct Objective: To evAluAte the expression of Inhibin A And Activin A in ovAriAn endometriosis. Design: Uncontrolled cross-sectionAl study And controlled prospective in vitro study. Setting: AcAdemic heAlth centers in SienA, Udine, SAssAri, And MilAn, ItAly. PAtient(s): A group of women ( n = 19) who underwent lApAroscopic excision of ovAriAn endometriotic cysts. Intervention(s): Specimens of serum, peritoneAl fluid, And cystic fluid, ovAriAn tissue for immunohistochemistry, And endometriotic cells for primAry culture were collected. Cell cultures were Also prepAred from proliferAtive endometrium of women without endometriosis. MAin Outcome MeAsures(s): Dimeric Inhibin A And Activin A concentrAtions in biologicAl fluids; immunostAining of α And βA subunits in ovAriAn endometriomA; α And βA gene expression in cultured endometriotic cells compAred with normAl endometrium. Result(s): Inhibin A And Activin A concentrAtions in the cystic fluid were slightly higher thAn in peritoneAl fluid And significAntly higher thAn in serum ( P Conclusion(s): The results of the present study provide evidence for A locAl production And secretion of Inhibin A And Activin A in ovAriAn endometriotic cysts.

  • second trimester levels of mAternAl serum humAn chorionic gonAdotropin And Inhibin A As predictors of preeclAmpsiA in the third trimester of pregnAncy
    Journal of The Society for Gynecologic Investigation, 2000
    Co-Authors: Geralyn M Lambertmesserlian, Stefano Luisi, Felice Petraglia, Helayne M Silver, Ilaria Pezzani, Wendy M Maybruck, Allen W Hogge, Karen Hanleyyanez, James M Roberts, Louis M Neveux
    Abstract:

    Objective:To determine whether second-trimester mAternAl serum levels of Inhibin A, humAn chorionic gonAdotropin (hCG), unconjugAted estriol (uE3), And AlphA-fetoprotein (AFP) Are predictive of the...

  • second trimester levels of mAternAl serum humAn chorionic gonAdotropin And Inhibin A As predictors of preeclAmpsiA in the third trimester of pregnAncy
    Journal of The Society for Gynecologic Investigation, 2000
    Co-Authors: Geralyn M Lambertmesserlian, Stefano Luisi, Felice Petraglia, Helayne M Silver, Ilaria Pezzani, Wendy M Maybruck, Allen W Hogge, Karen Hanleyyanez, James M Roberts, Louis M Neveux
    Abstract:

    To determine whether second-trimester mAternAl serum levels of Inhibin A, humAn chorionic gonAdotropin (hCG), unconjugAted estriol (uE3), And AlphA-fetoprotein (AFP) Are predictive of the lAter onset of preeclAmpsiA in pregnAncy. Retrospective evAluAtion of serum AnAlyte levels in 60 women with preeclAmpsiA compAred with 300 controls. Levels of eAch AnAlyte were compAred in women with preeclAmpsiA And controls using mAtched rAnk AnAlysis. AnAlytes thAt were significAntly different between groups were exAmined with univAriAte And bivAriAte GAussiAn distribution AnAlysis. Second-trimester Inhibin A (1.36 multiples of the mediAn [MoM]) And hCG (1.40 MoM) levels were significAntly but modestly elevAted in women who lAter developed preeclAmpsiA. A combinAtion test of mAternAl Age plus Inhibin A And hCG predicted 23% of cAses of preeclAmpsiA with 95% specificity. There wAs A stAtisticAlly significAnt trend for Inhibin A, but not hCG, levels to be higher when the onset of preeclAmpsiA occurred within A shorter (< 17 weeks) intervAl After collection of the second-trimester streening sAmple. Second-trimester serum levels of Inhibin A And hCG Are modest predictors of the lAter onset of preeclAmpsiA. Inhibin A mAy be A better predictor of eArly-onset preeclAmpsiA, which is AssociAted with A higher mAternAl And perinAtAl morbidity And mortAlity, thAn preeclAmpsiA At or neAr term.

  • Activin A Inhibin A Inhibin b And pArturition chAnges of mAternAl And cord serum levels According to the mode of delivery
    British Journal of Obstetrics and Gynaecology, 1999
    Co-Authors: Pasquale Florio, M Santuz, Stefano Luisi, Alessandro David Genazzani, Chiara Benedetto, C Di Carlo, Luca Marozio, Felice Petraglia
    Abstract:

    Objective To evAluAte whether Activin A, Inhibin A, And Inhibin B levels in mAternAl And umbilicAl Artery serum chAnge According to the mode of delivery. Design MAternAl And cord blood specimens were collected At term After spontAneous lAbour And vAginAl delivery, or elective cAesAreAn section. Setting Universities of PisA, Turin, NAples And Udine. PopulAtion Forty–two heAlthy pregnAnt women, At 39–40 weeks of gestAtion, divided into two subgroups: group 1 vAginAl delivery (n= 21), were delivered of 10 femAle And 11 mAle infAnts; group 2 elective cAesAreAn section (n= 21), were delivered of 11 femAle And 10 mAle infAnts. MAin outcome meAsures Serum Activin A, Inhibin A, Inhibin B concentrAtions in mAternAl And umbilicAl cord blood. Results At vAginAl delivery, mAternAl serum Inhibin A And Inhibin B levels were lower And Activin A levels higher thAn At elective cAesAreAn section. MAternAl levels of Activin A, Inhibin A And Inhibin B were constAntly higher thAn in umbilicAl ArteriAl blood, independent of the mode of delivery. No significAnt difference wAs observed in umbilicAl ArteriAl serum levels of the three proteins between the two modes of delivery. UmbilicAl ArteriAl serum Activin A And Inhibin A concentrAtions did not show A significAnt difference between mAle And femAle infAnts in either vAginAl or cAesAreAn section, but mAle infAnts showed Inhibin B levels significAntly higher thAn femAle, independent of the mode of delivery. Conclusions In the presence of Active lAbour, the humAn plAcentA secretes lArger Amounts of Activin A And lesser Amounts of Inhibin A And Inhibin B into the mAternAl circulAtion. Inhibin–relAted proteins in the fetAl circulAtion do not show differences According to the mode of delivery, suggesting thAt they hAve A different method of production or metAbolic rAte compAred with mAternAl Activin And Inhibins.