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PubMed2004

Gene expression and protein localisation for activin-A, follistatin and activin receptors in goat ovaries.

We studied the protein and mRNA expression of activin-A, follistatin and activin receptors in goat ovaries to find evidence of their possible role in ovarian activity, particularly in the various stages of follicle development. Ovaries of cyclic goats were collected and then either fixed in paraformaldehyde for immunohistochemical localisation of activin-A, follistatin, activin receptors IIA/B (ActR-IIA/B) and IA (ActR-IA) proteins or used to obtain samples to demonstrate mRNA expression of activin-A (betaA subunit), follistatin, ActR-IIA, -IIB, -IA and -IB, using RT-PCR. For this latter goal, primordial, primary and secondary follicles were isolated mechanically, washed to remove the stromal cells and then used for RT-PCR. In addition, oocytes, cumulus, mural granulosa and theca cells from small (<3 mm) and large (3-6 mm) antral follicles, luteal cells and surface epithelium were collected to study mRNA expression. Activin-A and follistatin proteins were found in oocytes of all follicle classes, granulosa cells from the primary follicle stage onwards, theca cells of antral follicles, corpora lutea and ovarian surface epithelium. In antral follicles, these proteins were detected both in cumulus and mural granulosa cells. ActR-IIA/B protein was found at the same follicular sites, and also in granulosa cells of primordial follicles onward. The localisation of ActR-IA corresponded with that of ActR-IIA/B, but the former protein was absent in the theca of large antral follicles. The mRNAs for activin-A (betaA subunit), follistatin, and ActR-IIA, -IIB, -IA and -IB were detected at all follicular and cellular types studied, except that ActR-IIB was not found in follicles that had not developed an antrum yet. In conclusion, in goat ovaries, transcripts of activin-A (betaA subunit), its receptors and its binding protein follistatin are expressed and their proteins formed at all follicular stages and in corpora lutea. These findings indicate a role of activin-A in the local regulatory system during the entire follicular development and during luteal activity.

Activin Receptors↗
PubMed2000

Activin receptors are expressed on human lung fibroblast and activin A facilitates fibroblast-mediated collagen gel contraction.

Activin A is a member of the transforming growth factor-beta superfamily that exerts its diverse biological effects through bindings to activin specific transmembrane serine/threonine kinase receptors. The fibroblast-mediated contraction of a collagen gel is thought to be a model of part of the wound-repair response and tissue contraction. In this study, we found the expression of activin type I receptors (ActR-I and ActR-IB) and type II receptor (ActR-II) on human fetal lung fibroblasts (HFL-1) by RT-PCR and immunocytochemistry. We also examined the effects of activin A on the HFL-1-mediated collagen gel contraction. Activin A stimulated collagen gel contraction in a dose dependent manner and its effect was abolished by an activin-binding protein, follistatin, that specifically suppresses activin A activities. This study demonstrated that ActR-I, ActR-1B and ActR-II are expressed on human fetal lung fibroblast and that activin A regulates fibroblast-mediated collagen gel contraction, suggesting that activin A might contribute to human lung fibroblast activities and structural remodeling observed in pulmonary fibrosis.

Activin Receptors↗
PubMed1999

Identification of two amino acids in activin A that are important for biological activity and binding to the activin type II receptors.

Activins are members of the transforming growth factor-beta family of growth and differentiation factors. In this paper, we report the results of a structure-function analysis of activin A. The primary targets for directed mutagenesis were charged, individual amino acids located in accessible domains of the protein, concentrating on those that differ from transforming growth factor-beta2, the x-ray crystal structure of which is known. Based on the activities of the recombinant activin mutants in two bioassays, 4 out of 39 mutant proteins (D27K, K102A, K102E, and K102R) produced in a vaccinia virus system were selected for further investigation. After production in insect cells and purification of these four mutants to homogeneity, they were studied in bioassays and in cross-linking experiments involving transfected receptor combinations. Mutant D27K has a 2-fold higher specific bio-activity and binding affinity to an ActRIIA/ALK-4 activin receptor complex than wild type activin, whereas mutant K102E had no detectable biological activity and did not bind to any of the activin receptors. Mutant K102R and wild type activin bound to all the activin receptor combinations tested and were equipotent in bioassays. Our results with the Lys-102 mutants indicate that the positive charge of amino acid 102 is important for biological activity and type II receptor binding of activins.

Activin Receptors, Type II↗
PubMed1995

Expression and localization of activin beta A-subunit and activin receptors in TM3, a mouse Leydig cell line.

We have determined whether TM3 cells, a cell line derived from a murine Leydig cell tumor, (a) transcribe messenger RNAs encoding the beta A-subunits of inhibin/activin, and activin receptors I, II, and IIB, and (b) produce activin-A protein. Messenger RNAs for inhibin/activin beta A-subunits and activin receptors II, and IIB in TM3 cells were localized and expressed using in situ hybridization and the reverse transcription-polymerase chain reaction (RT-PCR) analysis, respectively. The identify of the RT-PCR products was confirmed by DNA sequencing of PCR products. Immunocytochemically, activin-A was localized in these cells. We observed that messenger RNAs encoding activin beta A-subunit as well as activin receptors II, and IIB were expressed and activin protein was produced by TM3 cells. These findings suggest that activin-A may have autocrine functions in TM3 cells and that activin-A may be involved in regulating the growth and differentiation of mouse Leydig cells.

Activin Receptors↗
PubMed2002

Expression of activin receptors, follistatin and betaglycan by human endometrial stromal cells; consistent with a role for activins during decidualization.

Decidualization of the human endometrium is critical for implantation, but the mechanisms involved are largely unknown. Activin subunits are expressed in endometrium during decidualization. From its known actions in cell differentiation and tissue remodelling, we hypothesized that activin A is involved in the paracrine regulation of decidualization. We examined the expression of activin receptors (ActRs) by semi-quantitative and real-time RT-PCR. mRNA for all ActR subtypes (Ia, Ib, IIa and IIb) was detected in endometrium, with maximal expression in the early secretory phase and in early pregnancy. ActR protein was localized exclusively to stromal and endothelial cells. This expression pattern was confirmed by in-situ hybridization. Activin bioavailability is locally regulated by its binding protein, follistatin, and also by the antagonist, inhibin. Inhibin competition for ActRII binding is enhanced by the binding protein, betaglycan. Follistatin and betaglycan were also detected in the endometrium, localized to stromal and epithelial cells. This co-expression of activin subunits, receptors and binding proteins indicates that stromal cells are capable of responding to activin, and that there is tight local regulation of activin action within the endometrium. As activin production is up-regulated in decidual cells, this provides further evidence for an involvement of activins during stromal cell decidualization.

Activin Receptors↗
PubMed2003

Activin-A up-regulates type I activin receptor mRNA levels in human immortalized extravillous trophoblast cells.

Activin is known to play an important regulatory role in reproduction, including pregnancy. To further examine the role and signaling mechanism of activin in regulating placental function, the steady-state level of activin type I receptor (ActRI) mRNA in immortalized extravillous trophoblasts (IEVT) cells was measured using competitive PCR (cPCR). An internal standard of ActRI cDNA for cPCR was constructed for the quantification of ActRI mRNA levels in IEVT cells. ActRI mRNA levels were increased in a dose-dependent manner by activin-A with the maximal effect observed at the dose of 10 ng/ml. Time course studies revealed that activin-A had maximal effects on ActRI mRNA levels at 6 hours after treatment. The effects of activin-A on ActRI mRNA levels was blocked by follistatin, an activin binding protein, in a dose-dependent manner. In addition, inhibin-A inhibited basal, as well as activin-A-induced ActRI mRNA levels. These findings provide evidence, for the first time, that activin-A modulates ActRI mRNA levels in human trophoblast cells.

Activin Receptors, Type I↗
PubMed1999

Activin and inhibin binding to the soluble extracellular domain of activin receptor II.

Activins and inhibins belong to the transforming growth factor-beta-like superfamily of growth and differentiation factors that exert pleiotropic effects in many target tissues. Heteromeric association of activin with two structurally related receptor serine/threonine kinases, activin receptor types I and II, initiates downstream signaling events. The extracellular domain of type II mouse activin receptor (ActRII ECD) was expressed in the baculovirus system, purified in three steps by lectin affinity, anion exchange, and reverse phase chromatography, and further characterized by mass spectrometry. The reduction in the apparent size of the purified ActRII ECD on SDS-PAGE after treatment with glycosidases provided evidence for N- and O-linked oligosaccharides. Specific receptor/ligand complexes of [125I] activin A to ActRII ECD or [125I]ActRII ECD to activin A were analyzed by cross-linking and immunoprecipitation. Two major radiolabeled bands were observed on SDS-PAGE with mobilities consistent with the expected size of ActRII ECD/betaA or ActRII ECD/betaAbetaA. When inhibin A was cross-linked to [125I]ActRII ECD, a slower migrating complex corresponding to ActRII ECD/betaAalpha was also observed. The apparent dissociation constant (Kd) for activin A binding to ActRII ECD was 2-7 nM. This Kd value is approximately an order of magnitude greater than that of the full-length membrane-associated type II receptor. Treatment of cultured rat anterior pituitary cells with ActRII ECD attenuated FSH secretion in response to exogenous activin A or endogenous activin B. These data indicate that the soluble ActRII ECD has structural determinants that are sufficient for high affinity ligand binding.

Activin Receptors↗
PubMed2003

Down-regulation of activin, activin receptors, and Smads in high-grade breast cancer.

Activin and transforming growth factor (TGF)-beta, members of the TGF-beta superfamily of growth factors, have been implicated in both mammary gland development and breast carcinogenesis. TGF-beta is thought to be involved in the maintenance of mammary gland ductal architecture and postlactational involution. TGF-beta acts as both a tumor suppressor and has oncogenic capacities in breast cancer tissue. Activin is associated with growth modulation in glandular organs, and its receptors and signaling proteins are present and regulated during postnatal mammary gland development, primarily during the lactational phase. The presence of the major components of the activin signal transduction pathway in different pathologic grades of breast cancer tissue has not been described thoroughly, despite evidence from in vitro studies suggesting that activin can inhibit proliferation in breast cancer-derived cells. On the basis of the growth regulatory capacity of activin, we hypothesized that the components of this signal transduction system would be deregulated as breast cancer becomes more aggressive. To test this hypothesis, breast cancer samples were substratified by pathologic grade, a known prognostic marker for breast cancer, and then examined for the presence and cellular localization of activin ligand subunits (beta A- and beta B-), receptors (Act RIIA, Act RIIB, and Act RIB), and signaling proteins, Smads 2, 3, and 4, by immunohistochemistry and immunofluorescent analysis. Breast tissue from healthy patients undergoing reduction mammoplasty was also studied. The activin beta A-subunit was present in all of the tissues examined, whereas the beta B-subunit, activin type II receptors, and Smads were less evident in high-grade cancers. Significant correlations were made in breast cancer specimens between a decrease in nuclear Smad 3 abundance and high tumor grade, high architectural grade, larger tumor size, and hormone receptor negativity. Thus, activin signal transduction components are present in normal tissue and grade 1 cancer but down-regulated in high-grade cancer. The deregulation of this signal transduction system may be relevant to advancing oncogenic progression.

Activin Receptors↗
PubMed1994

Activin-like peptides in somatotrophs and activin stimulation of growth hormone release in goldfish.

Activin and inhibin, dimeric protein hormones originally isolated from mammalian gonads, are involved in the regulation of pituitary gonadotropin secretion. Using domain-specific antibodies against activin and inhibin alpha, beta A, and beta B subunits, the present study demonstrates that immunoreactive activin and inhibin subunits, especially beta A, exist in goldfish pituitary. Immunocytochemical staining with anti-gonadotropin-II and anti-growth hormone showed that the pituitary cells containing immunoreactive activin beta subunits are somatotrophs. This is different from the situation in mammals where it is the gonadotrophs that produce activin molecules within the pituitary. The staining with anti-beta B was overall weak compared to that with anti-beta A, but both appear to localize in the same cells. Strong immunostaining with the anti-inhibin alpha subunit was also observed in the goldfish pituitary; however, the immunoreactivity is dissociated from those of beta A and beta B, and mainly associated with nerve fibers in the neurointermediate lobe. Based on this evidence, it is suggested that the goldfish pituitary predominantly produced activin-like molecules. Both porcine activin and inhibin stimulate growth hormone release from perifused goldfish pituitary fragments. Taken together with our previous findings that porcine activin stimulates gonadotropin-II release in goldfish, and the fact that the somatotrophs and gonadotrophs are in close contact with each other in the goldfish pituitary, it is hypothesized that somatotroph-derived activin may exert paracrine actions on the adjacent gonadotrophs to stimulate gonadotropin release and autocrine actions on somatotrophs to stimulate growth hormone secretion. This also provides a mechanism for communication between these two pituitary cell types.

Activins↗
PubMed1994

The tissue distribution of activin beta A- and beta B-subunit and follistatin messenger ribonucleic acids suggests multiple sites of action for the activin-follistatin system during human development.

Activins have potent effects on early morphogenetic events during amphibian embryogenesis but no evidence for their role during human development other than their expression in steroidogenic tissues has been reported. We previously showed the expression of the activin type II and IIB receptor mRNAs in several tissues of the mid-gestational human fetus with highest expression levels in developing neural, muscular and exocrine glandular organs. We now report that the mRNA transcripts for activin beta A- and beta B-subunits and for the activin-binding protein follistatin are found co-expressed in several of these extragonadal tissues. Their mRNAs were detected by Northern analyses using specific single-stranded 32P-labeled cDNA probes. In the nervous system, both activin beta A- and beta B-subunit transcripts were expressed in the cerebrum and spinal cord. Follistatin was abundantly expressed in the spinal cord whereas weaker signals where observed in the cerebrum and cerebellum. In the muscular system, beta A-subunit was abundantly expressed in the heart but to a lesser extent in the skeletal muscle while the opposite was observed for follistatin. Follistatin, and activin beta A- and beta B-subunit mRNAs were also detected in developing kidney, salivary gland, liver, and adrenal. The predominance of beta A-subunit mRNAs in the bone marrow and beta B-subunit mRNAs in the salivary gland suggests specific roles for activin A and B, respectively, in these tissues. No hybridization signal was detected for the inhibin alpha-subunit in non-steroidogenic tissues indicating that, in contrast to activins and follistatin, the effects of inhibins may be restricted to the gonads and adrenals which are known to express high levels of the alpha-subunit transcript. Taken together, our results suggest that the activin-follistatin system regulates the development of several organ systems in the mid-gestational human fetus.

Abortion, Legal↗
PubMed2002

Biphasic regulation of activin A secretion by gonadotropins in cultured human ovarian granulosa-luteal cells leads to decreasing activin:inhibin ratios during continuing gonadotropin stimulation.

Pituitary gonadotropins mediate part of their effects on ovarian function via local hormones and growth factors produced by granulosa cells. Activins and inhibins are among these factors, and they have often opposite effects on various components of the reproductive system. The purpose of this study was to investigate the regulation of ovarian activin A secretion using cultured human ovarian granulosa-luteal cells as a model. The granulosa-luteal cells, obtained from women taking part in an in vitro fertilization program, were cultured and treated with FSH, LH, 8-bromo cAMP (8-BrcAMP, a protein kinase A activator) and 12-O-tetradecanoyl phorbol-13-acetate (TPA, a protein kinase C activator). Conditioned cell culture media were analyzed for activin A, inhibin A and progesterone concentrations with specific enzyme immunoassays. FSH and LH (1-100 IU/l) increased activin A secretion with 24 h of treatment (to 132% and 253% of control respectively; P<0.05 for both), but their effects were inhibitory in 48-h treatments (26% and 16% decreases respectively; P<0.05 for both). In the same experiments, FSH and LH increased inhibin A and progesterone secretion after both 24 and 48 h of treatment. 8-BrcAMP (0.1-100 muM) increased activin A in 24- and 48-h experiments (to 206% and 148% of control respectively; P<0.01 for both). Inhibin A and progesterone secretion were stimulated by 8-BrcAMP time- and dose-dependently. TPA increased activin A secretion dose-dependently (0.1-100 ng/ml) in both 24- and 48-h experiments. At 100 ng/ml concentration, it increased activin A up to 61-fold and inhibin A up to 16-fold of control in 24-h experiments. We conclude that gonadotropins regulate immunoreactive activin A secretion biphasically in cultured human granulosa-luteal cells: initial stimulation is followed by inhibition. In contrast, gonadotropins increase inhibin A and progesterone secretion continuously. Consequently, continuing gonadotropin stimulation leads to a decreasing activin:inhibin ratio, which may have a significant role in the local fine-tuning of ovarian steroidogenesis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Expression of activins and activin receptors in human retinoblastoma cell line Y-79.

Activin is a member of TGF beta family and is known to inhibit neuronal differentiation in certain tumor cell lines. In this study, the messenger RNA expression of activin subunits and activin receptors was characterized in retinoblastoma cell line Y-79 using the reverse transcription-polymerase chain reaction as well as in situ hybridization. The identity of the RT-PCR products was confirmed by DNA sequencing of PCR products. The activin protein production was determined by immunocytochemistry. We found that Y-79 cells transcribe mRNAs coding activin subunits and activin receptors and produce activin proteins. Our results imply that activin may have autocrine functions in these cells.

Activin Receptors↗
PubMed1998

The role of activin type I receptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells.

Activins transduce their signals by binding to activin type I receptors and activin type II receptors, both of which contain a serine/threonine kinase domain. In this study, we established stable transfectants expressing two types of activin receptors, ActRI and ActRIB, to clarify the role of these receptors in activin signalling for growth inhibition in HS-72 mouse B-cell hybridoma cells. Over-expression of ActRI suppressed activin A-induced cell-cycle arrest in the G1 phase caused by inhibition of retinoblastoma protein phosphorylation through induction of p21CIP1/WAF1, a cyclin-dependent kinase inhibitor, and subsequent apoptosis. In contrast, HS-72 clones that over-expressed ActRIB significantly facilitated activin A-induced apoptosis. These results indicate that ActRI and ActRIB are distinct from each other and that the ActRI/ActRIB expression ratio could regulate cell-cycle arrest in the G1 phase and subsequent apoptosis in HS-72 cells induced by activin A.

Activin Receptors, Type I↗
PubMed2006

Transgenic mice expressing dominant-negative activin receptor IB in forebrain neurons reveal novel functions of activin at glutamatergic synapses.

The transforming growth factor beta family member activin is an important regulator of development and tissue repair. It is strongly up-regulated after acute injury to the adult brain, and application of exogenous activin protects neurons in several lesion models. To explore the role of endogenous activin in the normal and acutely damaged brain, we generated transgenic mice expressing a dominant-negative activin receptor IB (dnActRIB) mutant in forebrain neurons. The functionality of the transgene was verified in vivo. Hippocampal neurons from dnActRIB mice were significantly more vulnerable to intracerebroventricular injection of the excitotoxin kainic acid than those from control littermates, indicating a crucial role of endogenous activin in the rescue of neurons from excitotoxic insult. Because dnActRIB is only expressed in neurons, but not in glial cells, activin affords protection at least in part through a direct action on endangered neurons. Unexpectedly, the transgenic mice also revealed a prominent novel role of activin in glutamatergic neurotransmission in the intact adult brain. Electrophysiologic examination of excitatory synapses onto CA1 pyramidal cells in hippocampal slices of dnActRIB mice showed a reduced NMDA current response, which was associated with impaired long term potentiation. This is the first demonstration that activin receptor signaling is essential to optimize the performance of neuronal circuits in the mature brain under physiological conditions.

Activin Receptors↗
PubMed1998

Activin subunit, follistatin, and activin receptor gene expression in the prepubertal female rat pituitary.

In the prepubertal female rat, a transient and selective increase in FSH secretion and mRNA expression by the pituitary gland occurs toward the end of the second postnatal week of life. To begin to investigate the possibility that activin may play a role in up-regulating FSH during this time, we have studied the ontogeny of the expression of the activin ss subunits, follistatin, and activin receptor subtypes in the prepubertal female rat pituitary. The levels of expression of ssA, ssB, and follistatin mRNAs were determined in the pituitary gland on postnatal days (PND) 8, 10, 12, 15, and 21 by semiquantitative reverse transcription-polymerase chain reaction. All values were compared to those of adult females killed on diestrus. mRNA levels of subunit ssA were significantly (p < 0.05) elevated on all postnatal days examined; ssB mRNA levels were elevated above adult levels only on PND 10 (p < 0.05). Follistatin mRNA was high on PND 8 (p < 0.05) and then decreased to adult levels. The level and distribution of activin receptor type II subtype mRNAs were determined by in situ hybridization. Activin receptor type II (Act RII) mRNA expression was diffusely expressed throughout all areas of the pituitary. Activin receptor type IIB (Act RIIB), on the other hand, was highly expressed by a subset of anterior pituitary cells. In situ hybridization for activin receptor subtype mRNAs was combined with immunocytochemistry to detect FSH-containing cells. We determined that in the infantile female pituitary, Act RII mRNA was generally not expressed in FSH-immunoreactive cells, while Act RIIB mRNA was expressed in FSH-immunoreactive cells. Act RII mRNA was lower on PND 10 and 15 when compared to PND 21 (p < 0.05), whereas Act RIIB mRNA expression did not change with age. These data suggest that the essential components of the activin regulatory system are present in the infantile female pituitary gland and thus may be involved in the differential regulation of FSH at this time.

Activin Receptors↗
PubMed1996

Activin signaling through activin receptor type II causes the cachexia-like symptoms in inhibin-deficient mice.

Activins and inhibins, members of the transforming growth factor-beta superfamily, are involved in diverse physiological and developmental processes. We have previously shown that mice deficient in alpha-inhibin develop gonadal sex cord-stromal tumors at an early age. The tumor development is rapidly followed by a wasting syndrome that includes severe weight loss, hepatocellular necrosis around the central vein, and depletion of the parietal cells in the glandular stomach. The liver histology in inhibin-deficient mice is similar to the pathological effects of short-term treatment of rats and mice with recombinant activin A. Consistent with these findings, we have shown that the gonadal tumors in the inhibin-deficient mice secrete high levels of activins. In addition, Northern blot analysis has localized activin receptor type II (ActRII) to the liver. Based on these studies, we postulated that tumor-produced activins act through ActRII to cause the wasting syndrome in inhibin-deficient mice. To test this hypothesis and determine the significance of elevated levels of activin signaling through ActRII in vivo, we generated compound homozygous mutant mice deficient in both alpha-inhibin and ActRII. Despite the continued development of gonadal sex cord-stromal tumors and elevated serum levels of activin A and B, the compound homozygous mutant mice suffered no unusual weight loss, and the stomachs and livers of the majority of the mice were histologically normal. These results demonstrate that increased levels of activin signaling through ActRII in hepatocytes and the glandular stomach causes the hepatocellular necrosis and depletion of parietal cells in the glandular stomach as well as the severe weight loss in vivo.

Activin Receptors↗
PubMed2006

Immunohistochemical localization of inhibin and activin subunits, activin receptors, and Smads in ovarian clear cell adenocarcinoma.

Our purpose was to examine the immunolocalization of inhibin, activin and the activin signaling system in ovarian clear cell adenocarcinoma tissue. Tissue samples of ovarian clear cell adenocarcinoma were collected from ten women. The patients' ages ranged from 41 to 71 years (mean +/- standard deviation; 53.4+/-9.9). Their surgicopathological staging was based on the criteria of the International Federation of Gynecology and Obstetrics (FIGO); there were 5 patients with stage I, 3 with stage II, and 2 with stage III. We examined the immunohistochemical localization of inhibin/activin alpha-subunit, betaA-subunit, activin A, and activin receptor types IA, IB, IIA, IIB, Smad2, Smad3 and Smad4 using an avidin-biotin peroxidase complex technique. With the antibodies against the betaA-subunit, and activin A, we observed positive immunoreactive staining in the cytoplasm of clear cell adenocarcinoma, whereas we did not observe any staining for the alpha-subunit of inhibin. We observed positive immunoreactive staining in the cell cytoplasm and surface with the antibodies against the activin receptors, types IA, IB, IIA and IIB. We observed positive immunoreactive staining in the cytoplasm and nucleus with the antibodies against the Smad2, Smad3 and Smad4. It is suggested that activin A, not inhibins, might be secreted by ovarian clear cell adenocarcinoma, and that an activin signal transduction pathway might exist in ovarian clear cell adenocarcinoma.

Activin Receptors↗
PubMed2002

The distribution of activin and activin receptors in gestational tissues across human pregnancy and during labour.

The aim of this study was to investigate localization and content of activin beta A-subunit and activin receptors in gestational tissues throughout pregnancy and in association with term labour. Placenta and fetal membranes were collected from women undergoing first and second trimester terminations and from women before and after term labour. Activin beta A-subunit and activin receptors IA, IB, IIA and IIB were studied by immunohistochemistry. Term tissues were analysed for activin A and follistatin content by ELISA and the presence of receptor proteins was assessed by Western hybridization. Activin beta A-subunit was localized to the syncytiotrophoblast and cytotrophoblast in placentae from all gestational ages, and to the amniotic epithelial and chorionic trophoblast layer at term. In placentae of first and second trimester, receptor proteins were localized to the syncytium, whereas at term, the distribution was confined predominantly to vascular endothelial cells of villous blood vessels. Receptor proteins in amnion were localized to some epithelial cells, mesenchyme and chorionic trophoblast. These findings suggest that activin A is secreted by and targets the placental syncytium and amniotic epithelium in early pregnancy, but at term targets the vascular endothelium of placenta and the fetal membranes. There were no differences with labour onset.

Activin Receptors↗