Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activin, a member of the transforming growth factor-beta superfamily, can regulate neuropeptide gene expression in the nervous system and in neuroblastoma cells. Among the neuropeptide genes whose expression can be regulated by activin is the gene encoding the neuropeptide vasoactive intestinal peptide (VIP). To investigate the molecular mechanisms by which activin regulates neuronal gene expression, we have examined activin's regulation of VIP gene expression in NBFL neuroblastoma cells. We report here that NBFL cells respond to activin by increasing expression of VIP mRNA. Activin regulates VIP gene transcription in NBFL cells through a 180-bp element in the VIP promoter that was previously characterized to be necessary and sufficient to mediate the induction of VIP by the neuropoietic cytokines and termed the cytokine response element (CyRE). We find that the VIP CyRE is necessary and sufficient to mediate the transcriptional response to activin. In addition, ciliary neurotrophic factor (CNTF), a neuropoietic cytokine, synergizes with activin to increase VIP mRNA expression and transcription through the VIP CyRE. Mutations in either the Stat (signal transducer and activator of transcription) or AP-1 sites within the CyRE that reduce the response to CNTF, also reduce the response to activin. However, mutating both the Stat and AP-1 sites within the wild-type CyRE, while reducing the separate responses to either activin or CNTF, eliminates the synergy between them. These data suggest that activin and CNTF, two factors that appear to signal though distinct pathways, activate VIP gene transcription through a common transcriptional element, the VIP CyRE.
Mol Endocrinol 2000 Mar
PMID:Synergy of activin and ciliary neurotrophic factor signaling pathways in the induction of vasoactive intestinal peptide gene expression. 1070 60

Inhibin A and B are dimeric proteins capable of suppressing FSH both in vitro and in vivo. The principal form in the male is inhibin B which is produced in the testis and circulates to inhibit pituitary FSH secretion. Activin A, B and AB are dimeric proteins that share the same beta subunits with the inhibins but, in contrast, stimulate FSH secretion. Although activin A circulates, castration does not lead to a decrease in serum concentrations, indicating that the testis is not the major source of activin A. In the circulation, the activins are bound to a structurally unrelated binding protein, follistatin, that neutralizes the biological actions of these proteins. The subunits of the inhibins/activins as well as follistatin are also produced locally within the pituitary and their levels can be modulated by testosterone and gonadotrophin releasing hormone as well as by autocrine mechanisms. Consequently, the output of FSH is dependent of the balance between local processes and the circulating feedback exerted by testosterone and inhibin. There is increasing data to support the local gonadal production of not only inhibin but also activin and follistatin by both germ cells and somatic cells such as the Sertoli cells. Evidence is accumulating to support the concept that these proteins exert local regulatory mechanisms in the testis.
Mol Cell Endocrinol 2000 Mar 30
PMID:The roles of inhibin and related peptides in gonadal function. 1077 90

Inhibins and activins are dimeric glycoproteins, member of the transforming growth factor beta (TGF beta) superfamily. The main source and targets of inhibins during the fertile age, in non pregnant women, are the ovaries, while during pregnancy placental production becomes predominant. Activin is produced from several organs: brain, ovary, uterus, placenta and spleen. During the menstrual cycles, inhibin B concentrations rise in the follicular phase with a peak after the ovulation peak of LH, inhibin A becomes predominant in the luteal phase. During reproductive life no significant change of activin A serum concentrations have been demonstrated. Inhibins and activins play an important biological role in the regulation of the HPO axis. The evaluation of inhibins and activins change is useful in understanding the pathophysiology of gynecological diseases and in the diagnosis of obstetric and gynecological pathologies.
Mol Cell Endocrinol 2000 Mar 30
PMID:Influence of non-gonadotrophic hormones on gonadal function. 1077 89

Using a combination of polymerase chain reaction (PCR) procedures, we have cloned and sequenced the rat activin beta(E) subunit cDNA. The putative protein corresponding to the prepro-activin beta(E) subunit was predicted to comprise 350 amino acids which, when cleaved between amino acid residues 236 and 237, would yield a mature polypeptide of approximately M(r) 12 500 with a predicted pI of 5.1. Two cDNA transcripts for activin beta(E) were identified; these differed by 738 bp in the 3'-untranslated region. Activin beta(E) mRNA transcripts were expressed only in rat liver and lung tissue as assessed by Northern blotting and PCR analysis. Relatively higher levels of both transcripts were found in the liver, whereas the lung contained lower levels that were detectable by PCR only. In situ hybridisation data showed that, within the liver, activin beta(E) mRNA was localised to hepatocytes. In vivo treatment with lipopolysaccharide as a means of activating the immune system and the hepatic acute-phase response resulted in stimulated activin beta(E) mRNA levels, compared with untreated, control rats. This increased expression was accompanied by a preferential increase in the amount of the long activin beta(E) transcript over the shorter transcript. These findings suggested that the two activin beta(E) mRNA transcripts may be products of alternative splicing events or use alternative polyadenylation sites which are differentially regulated during inflammation. These data provide evidence of a role for activin beta(E) in liver function and inflammation in the rat.
J Mol Endocrinol 2000 Jun
PMID:Cloning and regulation of the rat activin betaE subunit. 1082 34

In the process of amphibian development, an embryonic body plan is established through cell division, sequential gene expression, morphogenesis and cell differentiation. The mechanism of body patterning is complex and includes multiple induction events. Activin, a TGF-beta family protein, can induce several kinds of mesodermal and endodermal tissues in animal cap explants in a dose-dependent manner. In a recent study of the role of activin in organogenesis, we succeeded in raising a beating heart by treating animal caps with a high concentration of activin. Activin also participates in kidney organogenesis in combination with retinoic acid. An embryonic kidney induced by activin and retinoic acid in vitro can function in vivo when it is transplanted into a larva in which pronephros rudiments have already been removed. Further, the activin-treated animal caps clearly show organizer actions that are closely related to body patterning along the anteroposterior axis. These experiments will help to serve as a model system for understanding organogenesis and body patterning at the cellular and molecular levels.
Comp Biochem Physiol B Biochem Mol Biol 2000 Jun
PMID:In vitro control of organogenesis and body patterning by activin during early amphibian development. 1087 64

The hypothesis that activin and inhibin are autocrine/paracrine mediators of ovarian folliculogenesis has a solid basis. In mouse and rat models, granulosa cells (GC) of committed follicles express mRNA and protein for the activin/inhibin subunits and mRNA for the activin receptors (type I and II). Dimeric inhibin-A and -B are produced by postnatal ovarian cell dispersates and (GC) in culture. Similar levels of inhibin-A and -B are produced by postnatal ovarian cells, but thereafter as the ovary develops, inhibin-A becomes the predominant form. Activin was more effective than transforming growth factor-beta (TGF-beta) in enhancing follicle stimulating hormone (FSH)-stimulated inhibin production by ovarian cells. Evidence for a local regulatory role of estrogen in the ovary is also accumulating. Murine models of estrogen receptor (ERalpha or ERbeta) disruption produce mice with abnormal ovarian phenotypes. Female mice, which lack the capacity to produce estrogen (ArKO mice), have arrested folliculogenesis, no corpora lutea, elevated levels of luteinising hormone (LH), FSH and testosterone and are infertile. These data are consistent with autocrine/paracrine actions of activin in the early growth of committed follicles and estrogen in follicular maturation.
Mol Cell Endocrinol 2000 May 25
PMID:The roles of activins, inhibins and estrogen in early committed follicles. 1096 78

Development of germ cells during spermatogenesis is characterized by a complex series of differentiation events finally leading to the production of spermatozoa. Beside the main hormonal regulators, paracrine interactions are thought to play a major role in this process. Mitochondria in germ cells pass through unique alterations ranging from the 'typical' cristae-rich mitochondria found in spermatogonia to the 'condensed' form in pachytene spermatocytes. This study provides further support that paracrine factors produced by Sertoli cells, most likely activin A, are involved in germ cell differentiation as monitored by the maintenance of the physiological 'condensed' mitochondrial phenotype in primary spermatocytes. Culture of primary spermatocytes in Sertoli cell conditioned medium (SCCM) for 18 h resulted in the maintenance of a high percentage of 'condensed-type' mitochondria in comparison to cells cultured in Dulbecco's minimum essential medium (DMEM). Activin A, a product of Sertoli cells, showed at subnanogram concentrations a similar ability to SCCM to maintain a high percentage of spermatocyte mitochondria in the 'condensed' state, while inhibin had no effect. The addition of an antiserum specific for activin A resulted in a neutralization of the effect caused by activin A or SCCM. This strongly suggested that the active substance in SCCM was activin A. Taken together these data indicate that activin A is the first Sertoli cell product that has been identified to influence differentiation of male meiotic germ cells.
Mol Cell Endocrinol 2000 Oct 25
PMID:Activin maintains the condensed type of mitochondria in germ cells. 1106 57

17beta-Hydroxysteroid dehydrogenase type 1 (17HSD type 1) catalyzes the reduction of estrone (E(1)) to biologically more active estradiol (E(2)). In the present study, the effect of activin, inhibin, and follistatin on 17HSD activity and 17HSD type 1 expression in cultured, unluteinized rat granulosa cells was examined. Furthermore, the effects of these hormones on 17HSD type 1 expression were compared with the expression of P450 aromatase (P450arom). Rat granulosa cells were pre-incubated in serum-free media for 3 days, followed by a 2-day treatment with activin, inhibin, follistatin and 8-Br-cAMP. Activin in increasing concentrations appeared to effect a dose-dependent increase in 17HSD activity. In addition, increasing concentrations of activin also increased 17HSD type 1 mRNA expression. Addition of 8-Br-cAMP at concentrations of 0.25 and 1.5 mmol/l together with activin significantly augmented the stimulatory effects of activin alone in the cultured cells. Neither inhibin, nor follistatin, either alone or in combination with 8-Br-cAMP, had any notable effects on 17HSD activity and 17HSD type 1 expression. Preincubation of activin with increasing concentrations of follistatin significantly diminished the stimulatory effect of activin. In the presence of follistatin, activin did not significantly increase the 8-Br-cAMP-induced 17HSD activity and 17HSD type 1 expression. The culturing of granulosa cells in the presence or the absence of inhibin or follistatin with or without 8-Br-cAMP did not alter the effect of these peptides on P450arom expression in rat granulosa cells as judged by Northern blot analysis of total RNA. However, cAMP-induced P450arom expression was enhanced by activin treatment, except when follistatin was present. This is in line with the suggested role of follistatin as an activin-binding protein, which limits the bioavailability of activin to its membrane receptors. Thus, the results support the notion of a paracrine/autocrine role of activin in follicular steroidogenesis of growing follicles.
J Steroid Biochem Mol Biol
PMID:Activin-A, but not inhibin, regulates 17beta-hydroxysteroid dehydrogenase type 1 activity and expression in cultured rat granulosa cells. 1107 Mar 49

Activin, a member of the transforming growth factor beta (TGFbeta) superfamily of cytokines, inhibits cell proliferation in a variety of cell types. The functions of activin are mediated by type I and type II serine/threonine kinase receptors. The main type I receptor mediating activin signaling in human cells is ActRIB, also called Alk4. We have previously reported that several truncated Alk4 receptor isoforms are exclusively expressed in human pituitary tumors, and that the majority of such tumors did not exhibit activin-induced growth arrest in culture. We therefore studied the function of these truncated receptor isoforms. Transient expression of these truncated receptors inhibited activin-activated transcription from an activin-responsive reporter construct, 3TPLux. When each of these truncated Alk4 receptors was stably transfected into K562 cells, activin-induced expression of an endogenous gene, junB, was blocked, indicating that inhibition of gene expression also occurred at the chromosomal level. Furthermore, activin administration failed to cause growth inhibition and an increase of the G1 population in these cells. Coimmunoprecipitation experiments showed that the truncated Alk4 receptors formed complexes with type II activin receptors, but were not phosphorylated. These data indicate that the truncated activin type I receptors, predominantly expressed in human pituitary adenomas, function as dominant negative receptors to interfere with wild-type receptor function and block the antiproliferative effect of activin. This may contribute to uncontrolled pituitary cell growth and the development of human pituitary tumors.
Mol Endocrinol 2000 Dec
PMID:Truncated activin type I receptor Alk4 isoforms are dominant negative receptors inhibiting activin signaling. 1111 35

Activin and follistatin (FS) appear to play a role in the development of the skin and its appendages, in the inflammatory process, angiogenesis, and in wound healing. Although there is information on the expression of activin subunits and receptors in fibroblasts and keratinocytes, there are no reports on the regulation of FS expression in these cells. In the present study we analyzed the splicing variants of FS mRNAs in fibroblasts from genital and nongenital skin by RT-PCR and northern analysis, and examined the induction of FS mRNA and protein by hormones and growth factors in skin fibroblasts from human and nonhuman primates. FS mRNA was highly expressed in all fibroblast strains with similar expression regardless of donor species (human or monkey), donor age (neonate or adult), or the organ from which the fibroblast strains were established (skin or pituitary, genital or non-genital skin). Moreover, the band density corresponding to FS-288 was <5-10% of the value for FS-315 in skin fibroblasts as in all other tissues examined. Fibroblast FS mRNA and protein production were biphasically regulated by dexamethasone: low concentrations (0.01 and 0.1 nM) increased whereas higher concentrations (>1 nM) suppressed FS expression. On the other hand, androgens, activin and PACAP38 were without effect. These data establish cultured skin fibroblasts as a model to study FS gene expression in humans, and support a role for follistatin in the normal immune response and in the anti-inflammatory actions of glucocorticoids.
Mol Cell Endocrinol 2001 Feb 14
PMID:Follistatin production by skin fibroblasts and its regulation by dexamethasone. 1116 49


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