Inhibins and activins: roles in clinical practice

Wallace, Euan M.; Healy, David

doi:10.1111/j.1471-0528.1996.tb09541.x

Cited by 57 publications

(31 citation statements)

References 163 publications

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“…It is also accepted that the placenta is the major source of circulating activin in normal pregnancy (Wallace & Healy 1996). In this study, we have shown that placental activin A production is increased in preeclampsia and that placental activin A content is highly correlated with maternal serum levels.…”

Section: Discussionsupporting

confidence: 53%

Activin A and activin receptors in gestational tissue from preeclamptic pregnancies

Manuelpillai

Schneider-Kolsky

Dole

et al. 2001

Journal of Endocrinology

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Maternal serum activin A levels are elevated in women with preeclampsia. To explore whether this could be due, at least in part, to increased production by the gestational tissues, we have measured activin A in the serum of women with (n=23) or without preeclampsia (n=62) at 29-40 weeks of gestation and in placenta and fetal membranes from preterm preeclamptic (PT-PE, n=8), term preeclamptic (T-PE, n=10) and healthy term controls (T-C, n=10). We have also explored if there are associated changes in activin receptor Alk2, ActRII and ActRIIB in these tissues. The relative amounts of receptor proteins were measured by densitometry on Western blots and receptors and activin A subunit localised by immunohistochemistry in PT-PE, T-PE and T-C gestational tissues (n=8-10/group).Maternal serum activin A levels were significantly elevated in women with preeclampsia (multiples of the normal median (MoM)=3·5, P<0·0001, Mann-Whitney U test) compared with healthy women (median MoM=1·0). Compared with control tissues, the activin A content was significantly higher in preeclamptic placentae (P=0·001 and P=0·0005 for PT-PE and T-PE respectively, Mann-Whitney U test), but significantly lower in the amnion (P=0·005 and P=0·014 for PT-PE and T-PE respectively) and choriodecidua (P=0·009 for T-PE). The maternal serum activin A level in women with preeclampsia was significantly correlated with elevated placental production (P=0·01, Pearson's correlation). Receptor Alk2 protein levels were significantly elevated in T-PE placentae (P=0·0006, Mann-Whitney U test), ActRIIB levels were significantly lower in PT-PE placentae (P=0·01) and ActRII levels were significantly lower in PT-PE choriodecidua (P=0·0002) compared with controls. There were no apparent differences in the distribution of the A subunit and receptors Alk2, ActRII and ActRIIB between control and preeclamptic tissues.These findings suggest that elevated levels of activin A in the maternal circulation in association with preeclampsia are due, at least in part, to increased placental production, and that the regulation of activin synthesis in placenta and fetal membranes is differentially regulated. Further, the differences in activin receptor protein levels between preeclamptic and control placenta and choriodecidua suggest that activin A-induced regulation may be altered in preeclampsia.

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Section: Discussionsupporting

confidence: 53%

Activin A and activin receptors in gestational tissue from preeclamptic pregnancies

Manuelpillai

Schneider-Kolsky

Dole

et al. 2001

Journal of Endocrinology

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“…In pregnancy, the placenta is the major source of activin in the maternal circulation (de Kretser et al 1994, Qu & Thomas 1995, Wallace & Healy 1996, Fowler et al 1998, secreting predominantly activin A (Fowler et al 1998). Maternal serum levels of activin A increase from about mid-pregnancy to a peak close to term (Muttukrishna et al 1996, Fowler et al 1998, Schneider-Kolsky et al 2002, falling quickly after birth (Fowler et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress increases placental and endothelial cell activin A secretion

Mandang

Manuelpillai

Wallace

2007

Journal of Endocrinology

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Circulating levels of activin A are significantly increased in women with preeclampsia when compared with those with a normal pregnancy. The mechanisms underlying these increased levels are unknown. We undertook these studies to explore whether oxidative stress might be the mechanism. We exposed trophoblast explants, human umbilical vein endothelial cells (HUVECs) and peripheral blood monocytes to oxidative stress in vitro using xanthine/xanthine oxidase (X/XO), measuring activin A and isoprostane in conditioned media and mRNA for activin b A in explants and HUVECs. We also measured isoprostane and activin A in serum from 21 women with preeclampsia and from 20 women with a normal pregnancy. Treatment with X/XO significantly increased 8-isoprostane production from placental explants, HUVECs and monocytes, indicative of oxidative stress, and significantly increased activin A output from placental explants (139 . 1G27 . 4 per mg wet weight vs 322 . 9G 89 . 7 pg/ml per mg wet weight, PZ0 . 02) and from HUVECs (1 . 2G0 . 2 vs 3 . 2G1 . 8 ng/ml, PZ0 . 04). There was no effect on activin A output from monocytes. X/XO significantly increased b A mRNA in placental explants but not in HUVECs. Maternal plasma levels of 8-isoprostane and activin A were significantly higher in women with preeclampsia when compared with controls (333 . 8G70 vs 176 . 3G 26 . 2 pg/ml, PZ0 . 04 and 49 . 5G7 vs 13 . 1G1 . 2 ng/ml, P!0 . 001 respectively). In the women with preeclampsia, but not in those with a normal pregnancy, circulating levels of 8-isoprostane and activin A were significantly and positively correlated (r 2 Z0 . 72; P!0 . 001). These data suggest that oxidative stress may be one of the mechanisms underlying increased circulating activin A in preeclampsia.

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“…Inhibin is a peptide‐hormone composed of two disulfide‐linked subunits termed alpha and beta, both of which are produced by granulosa and theca cells of the ovary, and inhibin activity has also been described in testicular Sertoli cells and Leydig cells (19,20). The general consensus from the published literature is that inhibin α is a very sensitive immunohistochemical marker of most ovarian sex cord‐stromal tumors but inhibin β is of less value, because although usually positive in ovarian sex cord‐stromal tumors, most adenocarcinomas also exhibited immunoreactivity (17,21).…”

mentioning

confidence: 99%

Inhibin α and β expression in ovarian stromal tumors and their histological equivalences

Çiriş

Erhan

Zekioğlu

et al. 2004

Acta Obstet Gynecol Scand

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Inhibin is a heterodimeric protein hormone that appears to be a sensitive immunohistochemical marker of sex cord-stromal tumors. Although sex cord-stromal tumors can usually be distinguished from ovarian epithelial tumors or their metastases by morphology or by using antibodies against intermediate filaments, the diagnosis remains difficult in rare situations in such cases as sarcomatoid granulosa-theca cell tumors, ovarian small cell carcinomas, or soft-tissue sarcomas. The purposes of this study were to examine inhibin alpha and beta immunoreactivity in a wide range of gonadal stromal neoplasms and to assess its value in the differential diagnosis of problematic tumors. A total of 108 paraffin-embedded ovarian and extraovarian tumors were examined immunohistochemically by using anti-alpha inhibin and anti-beta inhibin. Inhibin alpha immunostaining was identified in 46 (81%) of 57 gonadal stromal tumors, one (14%) of seven endometrial stromal tumors, and one (50%) of two primary ovarian carcinoid tumors. Inhibin beta immunostaining was detected in 55 (96%) of 57 gonadal stromal tumors, two (29%) of seven endometrial stromal tumors, one (50%) of two dysgerminomas, and in all of two (100%) primary ovarian carcinoid tumors. Inhibin alpha expression was not detected in any ovarian surface epithelial tumor cells. Some surface epithelial tumors showed stromal inhibin alpha (15% of cases) and inhibin beta (48% of cases) positivity. Weak immunoreactivity for inhibin beta was found in most (83% of cases) ovarian surface epithelial tumors. Two ovarian Burkitt lymphomas were negative for inhibin alpha and beta. Inhibin alpha is a sensitive immunohistochemical marker of gonadal stromal tumors and is of value in the differential diagnosis of ovarian neoplasia. Inhibin beta is a nonspecific marker for ovarian neoplasms, showing expression on tumor and stromal cells of different epithelial or stromal tumors.

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Inhibins and activins: roles in clinical practice

Cited by 57 publications

References 163 publications

Activin A and activin receptors in gestational tissue from preeclamptic pregnancies

Activin A and activin receptors in gestational tissue from preeclamptic pregnancies

Oxidative stress increases placental and endothelial cell activin A secretion

Inhibin α and β expression in ovarian stromal tumors and their histological equivalences

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