The Uterine Myometrium Is a Target for Increased Levels of Activin A during Pregnancy

Draper, Lawrence B.; Chong, Huira; Wang, Eileen; Woodruff, Teresa K.

doi:10.1210/endo.138.7.5231

Cited by 23 publications

(9 citation statements)

References 13 publications

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“…Activin A and activin receptor subunit ActRIIA have previously been shown to be associated with apoptosis (Schwall et al 1993, Yasuda et al 1993, Hully et al 1994, Coerver et al 1996, Draper et al 1997. Our results indicate that locally produced activin A acts as an autocrine factor to regulate hepatocyte cell proliferation, however we failed to demonstrate changes in ActRIIA mRNA.…”

Section: Discussioncontrasting

confidence: 74%

βA- and βC-activin, follistatin, activin receptor mRNA and βC-activin peptide expression during rat liver regeneration

Gold¹,

Zhang²,

Wheatley³

et al. 2005

Journal of Molecular Endocrinology

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The mRNA expression of two activin growth factor subunits ( A-and C-activin), activin receptor subunits (ActRIIA, ActRIIB) and the activin-binding protein follistatin, and peptide expression of A-activin and C-activin subunits, were examined in regenerating rat liver after partial hepatectomy (PHx). Liver samples were collected from adult, male Sprague-Dawley rats, 12-240 h (n=3-5 rats per time point) after PHx or from sham-operated controls at the same time points. Hepatocyte mitosis and apoptosis were assessed histologically and by in situ cell death detection. RT and PCR were used to assess relative gene expression. A-and C-activin peptide immunoreactivity was assessed in liver and serum samples by western blotting, whereas cellular expression was investigated by immunohistochemistry, using specific monoclonal antibodies. A-and C-activin mRNA dropped to,50% of sham control values 12 h after PHx and remained at this level until 168 h post-PHx, when A-activin expression increased to three times sham control values and C-activin mRNA returned to pre-PHx levels. A peak in follistatin expression was observed 24-48 h post-PHx, coincident with an increase in hepatocyte mitosis. No changes were observed in ActRIIA mRNA, whereas ActRIIB expression paralleled that of A-activin mRNA. C-activin immunoreactive homo-and heterodimers were observed in regenerating liver and serum. Mitotic hepatocytes frequently contained C-activin immunoreactivity, whereas apoptotic hepatocytes were often immunoreactive for A-activin. We conclude that A-and C-activin subunit proteins are autocrine growth regulators in regenerating liver and when expressed independently lead to hepatocyte apoptosis or mitosis in a subset of hepatocytes.

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Section: Discussioncontrasting

confidence: 74%

βA- and βC-activin, follistatin, activin receptor mRNA and βC-activin peptide expression during rat liver regeneration

Gold¹,

Zhang²,

Wheatley³

et al. 2005

Journal of Molecular Endocrinology

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“…The reported concentrations of total follistatin through pregnancy have been somewhat inconsistent between assays and groups. Previous cross-sectional studies of maternal serum in pregnancy show that activin concentrations increase in women in the third trimester, with activin A being the predominant isoform in all pregnant women (Draper et al 1997, Petraglia 1997, Schneider-Kolsky et al 2000, Wang et al 2002. Woodruff et al (1997) reported that while total follistatin concentrations increased in late pregnancy, in all women there were no significant increases in the small percentages of free follistatin.…”

Section: Introductionmentioning

confidence: 90%

Follistatin serum concentrations during full-term labour in women – significant differences between spontaneous and induced labour

Rae

Hollebone²,

Chetty³

et al. 2007

Reproduction

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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 (nZ33), needed induction by amniotomy and IV oxytocin (nZ18) or underwent planned caesarean section (nZ10). 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 gestation were significantly different between groups. Those who had a spontaneous labour had concentrations higher than those who were induced. Similarly, those who were induced had concentrations higher than those who underwent a caesarean. In the spontaneous group, follistatin rose during labour, peaking at 57.9G5.48 ng/ml at O3 cm of cervical dilation, and after delivery follistatin decreased to 26.16G3.4 ng/ml at 24 h post-delivery. In induced patients follistatin continued increasing to peak following delivery at 26.9G3.0 ng/ml and decreased at O3 h post-delivery. Follistatin concentrations in caesarean section patients at 24 h post-surgery (18.53G3.74 ng/ml) were not different from that before the surgery and were comparable with the other two groups. Follistatin is clearly implicated in the onset of labour; however, further studies with a larger cohort of women are necessary to determine the nature of its role. Reproduction (2007) 134 705-711

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“…Converging lines of evidence suggest that activin is an important growth factor in pregnancy, such that activin probably acts as a paracrine factor until late in gestation when circulating levels of this hormone increase dramatically (Woodruff & Mather 1995. Activin subunits are synthesized by the trophoblast cells (Petraglia et al 1992) and activin binding occurs in pregnant myometrium and the adrenal gland (Draper et al 1997). Alterations in activin levels have been associated with disease states such as pre-eclampsia (Muttukrishna et al 1997, Grobman & Wang 2000.…”

Section: Introductionmentioning

confidence: 99%

Activin signal transduction in the fetal rat adrenal gland and in human H295R cells

Ey²,

Woodruff³

2003

Journal of Endocrinology

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The presence of activin A and its effects have previously been documented in the adrenal gland, particularly in the human fetal adrenal gland and the rat adrenal gland. The primary signaling pathway of activin involves interactions between receptor and intracellular (Smad) proteins that have not been completely described in the adrenal gland. In this study, we demonstrate that the components of the activin signaling cascade are present in two complementary models, the fetal rat adrenal gland and the human adrenocortical cell line, H295R, by means of RT-PCR, western analysis, and immunoprecipitation techniques. Using the cell line, activin signaling was analyzed using an activin-responsive reporter gene, p3TP-luc, and luciferase assays to assess transcriptional activity with co-expression of the different activin receptors and Smads to demonstrate the functionality of the signaling cascade.In the fetal rat adrenal gland, the relative amounts of mRNA of the type II receptors, RII and RIIB, were regulated by gestational age, such that the RIIB levels increased after birth while RII levels fell. Using immunodetection techniques, the activin receptors and the different Smad proteins were detected in the rat fetal adrenal glands. Notably, the presence of Smad4 protein is significantly increased after birth in the rat adrenal gland. RT-PCR established a similar profile in the H295R cells. Using p3TP-luc, the H295R cells show transcriptional activation of this activin-responsive reporter in the presence of activin A. Co-expression of type I and type II receptors as well as Smads, results in ligand-independent transcriptional activity in addition to an activin-stimulated response. In determining activin's effects on adrenal function, adrenal steroid production was evaluated by incubation of the H295R cells with increasing doses of activin A and inhibin A, resulting in a detectable increase in P450c17 expression. Co-incubation of activin A with follistatin diminishes this response.These results are consistent with a role for activin A in the adrenal gland by demonstrating that the elements of the activin signaling pathway are present, intact, and functional. This suggests that in the adrenal gland the components of the activin receptor/Smad pathway are dynamically changing in the transition from fetal to neonatal life, and are important to the function of this organ.

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The Uterine Myometrium Is a Target for Increased Levels of Activin A during Pregnancy

Cited by 23 publications

References 13 publications

βA- and βC-activin, follistatin, activin receptor mRNA and βC-activin peptide expression during rat liver regeneration

βA- and βC-activin, follistatin, activin receptor mRNA and βC-activin peptide expression during rat liver regeneration

Follistatin serum concentrations during full-term labour in women – significant differences between spontaneous and induced labour

Activin signal transduction in the fetal rat adrenal gland and in human H295R cells

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