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)

cDNA encoding the extracellular domain of the rat activin receptor was cloned using the polymerase chain reaction (PCR). This cDNA is highly homologous to cDNA encoding the extracellular domain of the mouse activin receptor, whereas at the protein level the extracellular domains of both receptors are identical. Employing this cDNA as a probe in Northern blot analysis, expression of two activin receptor mRNAs (6 kb and 4 kb) was observed, in testes of immature and mature rats. Between day 21 and 28 of postnatal development, a large increase in testicular expression of the 4 kb mRNA was found, suggesting expression of this activin receptor mRNA in germ cells. The 4 kb mRNA was indeed present in isolated pachytene spermatocytes and round spermatids, but was absent in elongating spermatids. Sertoli cells obtained from immature and mature rats expressed both the 6 kb and 4 kb mRNAs, whereas the expression of these mRNAs in Leydig cell preparations was very low. These results may imply that activin has multiple actions in the control of testicular function.
Mol Cell Endocrinol 1992 Jan
PMID:Activin receptor mRNA expression in rat testicular cell types. 131 57

Establishment of the body pattern in all animals, and especially in vertebrate embryos, depends on cell interactions. During the cleavage and blastula stages in amphibians, signal(s) from the vegetal region induce the equatorial region to become mesoderm. Two types of peptide growth factors have been shown by explant culture experiments to be active in mesoderm induction. First, there are several isoforms of fibroblast growth factor (FGF), including aFGF, bFGF, and hst/kFGF. FGF induces ventral, but not the most dorsal, levels of mesodermal tissue; bFGF and its mRNA, and an FGF receptor and its mRNA, are present in the embryo. Thus, FGF probably has a role in mesoderm induction, but is unlikely to be the sole inducing agent in vivo. Second, members of the transforming growth factor-beta (TGF-beta) family. TGF-beta 2 and TGF-beta 3 are active in induction, but the most powerful inducing factors are the distant relatives of TGF-beta named activin A and activin B, which are capable of inducing all types of mesoderm. An important question relates to the establishment of polarity during the induction of mesoderm. While all regions of the animal hemisphere of frog embryos are competent to respond to activins by mesoderm differentiation, only explants that include cells close to the equator form structures with some organization along dorsoventral and anteroposterior axes. These observations suggest that cells in the blastula animal hemisphere are already polarized to some extent, although inducers are required to make this polarity explicit.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1992 Jun
PMID:The role of growth factors in embryonic induction in Xenopus laevis. 135 52

The regulation of steady-state follistatin mRNA levels by different pituitary hormones and peptide factors was examined in granulosa cell cultures derived from diethylstilboestrol-treated immature rats. Cytosolic RNA from cell cultures was prepared by lysis and equal amounts of RNA from all samples were analysed with a solution-hybridization assay using a 32P-labelled antisense probe corresponding to a part of exon 5 together with a part of the 5' end of exon 6 of the rat follistatin gene. In addition, a specific 35S-labelled probe for cyclophilin was used as an internal standard. The results show that 5 micrograms FSH/l for 24 to 72 h stimulated steady-state follistatin mRNA levels, reaching levels 18.5-fold higher than controls. LH (0.2-100 micrograms/l) had only minor effects on follistatin mRNA levels in FSH-primed granulosa cells and prolactin, GH and IGF-I did not show any significant effects. Activin raised basal as well as FSH-stimulated steady-state follistatin mRNA levels up to ten- and twofold above controls respectively, whereas epidermal growth factor was found to inhibit FSH-stimulated follistatin mRNA levels in a dose-dependent manner. It is concluded that follistatin mRNA levels in granulosa cells are regulated by FSH rather than LH, and that the stimulation by FSH can be inhibited by epidermal growth factor but enhanced by activin. Activin alone was also capable of stimulating follistatin mRNA.
J Mol Endocrinol 1992 Oct
PMID:Regulation of steady-state follistatin mRNA levels in rat granulosa cells in vitro. 141 85

The secretion of inhibin and inhibin-related proteins by testicular Leydig cells was studied by estimation of inhibin immunoreactivity and bioactivity in spent media of preparations of immature and mature rat Leydig cells and of tumor Leydig cells. Immature and mature rat Leydig cells expressed inhibin alpha-subunit mRNA and secreted immunoreactive inhibin. The immunoreactive material did not contain inhibin bioactivity as measured by an in vitro rat pituitary bioassay system. Results of pulse labeling with [35S]methionine followed by immunoprecipitation indicated that the inhibin-related proteins secreted by the immature Leydig cell preparations are 26 kDa and 44 kDa molecules. Mature rat Leydig cells only secreted the 44 kDa inhibin-related protein. Tumor Leydig cells (rat H540 and mouse MA10) secreted immunoreactive and bioactive inhibin, which could be immunoneutralized by an antibody against inhibin. In the culture medium of some H540 tumor Leydig cells 26 kDa and 42 kDa inhibin-related proteins and 30 kDa inhibin were detected. In culture medium of other H540 tumor Leydig cells, not secreting bioactive inhibin, only 26 kDa and 42 kDa inhibin-related proteins were found. No activin bioactivity was detected in culture media of immature rat Leydig cells, H540 and MA10 tumor Leydig cells. It is concluded that normal Leydig cells secrete inhibin alpha-subunits, while Leydig cell tumors can also secrete bioactive inhibin. Neither normal Leydig cells nor Leydig cell tumors produce activin.
Mol Cell Endocrinol 1992 Feb
PMID:Testicular Leydig cells in vitro secrete only inhibin alpha-subunits, whereas Leydig cell tumors can secrete bioactive inhibin. 154 6

The complexity of corticotropic cell regulation by multiple central and peripheral factors is well recognized. The present study provides evidence for the participation of an additional factor in the regulation of this cell type of the anterior pituitary. Using the clonal AtT20 cell line as a model for corticotropes, homodimeric activin-A was observed to suppress basal ACTH secretion and POMC mRNA accumulation by approximately 50%. These effects required prolonged treatment with activin-A and were concentration dependent; the half-maximum concentration was in the range of 30-50 pM. Consistently, AtT20 cells were found to express specific high affinity binding sites for [125I]activin-A. The simultaneous addition of inhibin-A along with increasing concentrations of activin-A did not alter the characteristics of the inhibition of ACTH secretion by activin-A alone. This is in contrast to observations with gonadotropes of the anterior pituitary as well as a number of other cell types in which inhibin-A can partially antagonize the biological actions of activin-A. The results may suggest the participation of a subclass of activin receptors that mediate effects on ACTH secretion and POMC mRNA accumulation. As previously shown, the incubation of AtT20 cells with a synthetic glucocorticoid, dexamethasone, attenuated basal ACTH secretion and POMC expression in a concentration-dependent manner. The inhibition of both of these parameters by activin-A, however, was independent of glucocorticoids, because the two agents were additive in their actions. In addition to effects on secretion and mRNA levels, treatment with activin-A also inhibited the rate of proliferation of AtT20 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1991 Oct
PMID:Activin-A inhibits proopiomelanocortin messenger RNA accumulation and adrenocorticotropin secretion of AtT20 cells. 166 77

Activin, a disulfide-linked polypeptide dimer first isolated from gonadal tissue extracts, has amino acid sequence and structural homology with transforming growth factor beta (TGF beta). Along with other activities, TGF beta regulates replication and differentiation and interacts with a defined set of binding sites on isolated bone cells. To determine if activin shares these properties, recombinant human activin-A (A-chain homodimer) was examined in osteoblast-enriched cultures obtained from fetal-rat parietal bone. After 23 h of treatment, 60 to 6,000 pM activin-A increased the rate of [3H]thymidine incorporation into DNA 1.5- to 4.0-fold, and at 600 to 6,000 pM, it enhanced the rate of [3H]proline incorporation into collagen and noncollagen protein by up to 1.7-fold. Like earlier studies with TGF beta in primary osteoblast-enriched cultures, the stimulatory effects of activin-A on DNA and protein synthesis were opposed by parathyroid hormone, and the influence of activin-A on collagen synthesis was independent of cell replication. Binding studies with 125I-activin-A indicated approximately 8,000 high-affinity (Kd = 0.4 nM) and 300,000 low-affinity (Kd = 40 to 50 nM) binding sites per cell. Polyacrylamide gel analysis revealed 125I-activin-A-binding complexes of Mr greater than 200,000 and 73,000 which did not appear to correspond to primary TGF beta-binding sites. These results indicate that activin-A produces TGF beta-like effects in bone and that some of these effects may be mediated, at least in part, by distinct activin receptors on bone cells.
Mol Cell Biol 1991 Jan
PMID:Activin-A binding and biochemical effects in osteoblast-enriched cultures from fetal-rat parietal bone. 184 21

Little information is available on the effects of activin and inhibin on the synthesis and secretion of pituitary gonadotrophins in species other than the rat. In this in-vitro study, ovine pituitary cell cultures derived from immature sheep were used to investigate the effects of recombinant human activin-A and native Mr 32,000 bovine inhibin on basal and gonadotrophin-releasing hormone (GnRH)-induced release of FSH and LH. Residual cellular contents of FSH and LH were also determined, allowing total content/well to be calculated. Activin-A promoted a dose-dependent increase in basal (+72%; P less than 0.001) and GnRH-induced (+25%; P less than 0.001) release of FSH as well as in the residual cell content (+114%; P less than 0.001) and total FSH content/well (+67%; P less than 0.001). Conversely, inhibin significantly (P less than 0.001) suppressed each aspect of FSH production examined, confirming that in sheep, as in rats, activin and inhibin exert opposing effects on pituitary FSH production. In contrast to the rat, however, in which activin is reported to have no effect on LH secretion, exposure of sheep pituitary cells to activin-A promoted a dose-dependent suppression (-42%; P less than 0.001) of GnRH-induced LH release. This was associated with a corresponding increase (P less than 0.001) in residual cellular content of LH. Consistent with a previous report from this laboratory, inhibin had the opposite effect and significantly enhanced (+47%; P less than 0.001) GnRH-induced LH release. This was associated with a corresponding fall (P less than 0.01) in residual cellular content of LH.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1991 Apr
PMID:Inverse effects of activin and inhibin on the synthesis and secretion of FSH and LH by ovine pituitary cells in vitro. 190 34

Direct roles of follicle-stimulating hormone (FSH)-suppressing protein (FSP) and activin in regulation of ovarian granulosa cell differentiation have been reported recently. The present study further investigated the effects of these peptides on steroidogenesis and inhibin production as well as cAMP generation in cultured granulosa cells from immature, diethylstilbestrol (DES)-treated rats. In the presence of FSH (20 ng/ml) and activin (30 ng/ml), which enhanced FSH-induced aromatase activity, progesterone production and inhibin production, FSP (1-100 ng/ml) reversed the stimulating activities of activin in a dose-dependent manner. In addition, activin reversed the inhibitory effects of FSP on FSH-induced aromatase activity and inhibin production. In the presence of FSH, activin enhanced FSH-stimulated extracellular cAMP accumulation, and FSP caused a reduction in extracellular cAMP. Activin but not FSP also stimulated basal cAMP level. In the presence of forskolin, a potent stimulant of adenyl cyclase activity which stimulated extracellular cAMP, aromatase activity, progesterone production and inhibin production, activin augmented the effect of forskolin on all four parameters, whereas FSP significantly enhanced progesterone production without changing the other three parameters. Our findings suggest that activin action on rat granulosa cells may be mediated via regulation of cAMP generation. The action of FSP and FSH and/or activin-dependent, consistent with either an action as an activin binding protein or by a direct action of FSP on the granulosa cells.
Mol Cell Endocrinol 1991 Aug
PMID:Interactions between activin and follicle-stimulating hormone-suppressing protein and their mechanisms of action on cultured rat granulosa cells. 193 50

The biosynthesis and intracellular processing of the polypeptide precursor of the beta A-chain of the fertility hormone inhibin were assessed by infecting a wide spectrum of cell types with a recombinant vaccinia virus. Most cell lines, including follicular granulosa cells, secrete both prohormone and mature hormone as homodimers (activin) composed of disulfide-linked subunits of 54 kDa (proactivin-A) and 14 kDa (activin-A), respectively, and a small amount of prohormone-mature hormone heterodimers. Mature activin is secreted from mouse pituitary cells (AtT-20), while pig kidney cells [PK(15)] secrete mostly proactivin. More prohormone is secreted in the presence of NH4Cl, suggesting that prohormone processing is facilitated by low pH. Proactivin-A is not a ligand for the mannose-6-phosphate/insulin growth factor-II receptor. The recombinant activin stimulates FSH release from pituitary cells and differentiates erythroleukemia cell lines in vitro.
Mol Endocrinol 1990 Aug
PMID:Expression and processing of the activin-A/erythroid differentiation factor precursor: a member of the transforming growth factor-beta superfamily. 196 71

The gene encoding the inhibin/activin beta B subunit was isolated from a Booroola Merino ewe which had two copies of the unidentified fertility gene. Both the DNA sequence (greater than 87%) and amino acid sequence (greater than 93%) were highly homologous to those of the human and rat genes. The upstream region of the gene was similar to that of the human and rat genes, having SP1 binding sites and no TATA or CAAT boxes and, like that of the rat, but unlike that of the human gene, no cyclic AMP response elements, suggesting that the beta B gene of sheep and rats is regulated differently from that of man.
J Mol Endocrinol 1991 Feb
PMID:Cloning of the inhibin/activin beta B subunit gene from the Booroola merino sheep. 201 59


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