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)

The acquisition of follicle-stimulating hormone (FSH) receptors during follicogenesis is believed to be a key event in the subsequent development of the follicle. We have examined the effect of FSH on FSH receptor mRNA in cultured rat granulosa cells by means of FSH receptor cRNA probe. Northern blot analysis indicated the existence of two predominant FSH receptor mRNA transcripts of approximately 5.5 and 2.4 kb in total RNA prepared from rat granulosa cells. Treatment of granulosa cell culture with FSH resulted in tentative suppression of FSH receptor mRNA level 2-6 h after treatment, with subsequent recovery at 24 h. Culture of granulosa cells for 6 h in the presence of increasing concentration of FSH resulted in a dose-dependent decrease in FSH receptor mRNA with a maximal suppression about 50% of control observed in response to 100 ng/ml FSH. We could not detect a similar effect on FSH receptor mRNA by 8-brom-adenosine 3,5-cyclic monophosphate (8-Br-cAMP; 0.2 mM) which showed continuous stimulation on FSH receptor mRNA during a similar time course. In this system, therefore, this transient down-regulation of FSH mRNA was not mediated by the cAMP pathway. Since the inhibitory effect of follistatin on activin-induced FSH binding to rat granulosa cells had been investigated, we studied the action of follistatin on the levels of activin-induced FSH receptor mRNA in rat granulosa cell culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1995 Feb 27
PMID:Regulation of follicle-stimulating hormone receptor messenger ribonucleic acid levels in cultured rat granulosa cells. 775 41

It is evident that members of several growth factor families are actively involved in embryogenesis from its earliest phases. Several reports also indicate the oviduct as a possible source of growth factors, suggesting an active role of this organ in mammalian embryonic development. The aim of this study was to investigate the presence of activin/inhibin subunits in bovine oviduct since activin is a well-characterised morphogen in amphibian development. The presence of transcripts for alpha, beta A, and beta B subunits was investigated by analysing oviduct epithelial cells mRNA with reverse transcription-polymerase chain reaction (RT-PCR). Moreover, antisera specific for the three subunits were used for the Western blot analysis of the proteins secreted by oviduct epithelial cells in vitro and for their immunohistochemical localisation in different oviductal regions. Oviduct epithelial cells expressed only the beta A-subunit gene. Immunoreactive material was present among in vitro secreted proteins, indicating that the transcript is translated into a polypeptide that has been localised in the epithelium of both the ampullary and isthmic tract of the organ. Consistent with these results, the antisera for the alpha and beta B subunits did not recognise any specific antigen either among secreted proteins or in the sections. These results indicate that beta A subunit gene is expressed in bovine oviduct epithelial cells, and the protein is secreted in vitro and can be found along the whole extension of the organ. In the absence of alpha or beta B subunits, this suggests that activin A is present in bovine oviduct.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1995 Mar
PMID:Activin beta A subunit is expressed in bovine oviduct. 777 38

The transforming growth factor beta (TGF-beta) superfamily includes several closely related peptides including the activins and inhibins. Since we recently reported that TGF-beta 1 and beta 2 are potent inducers of steroid 5 alpha-reductase (5 alpha R), we have now studied the effects of these other peptides using primary cultures of human scrotal skin fibroblasts. Recombinant human activin A or inhibin A were added to cultured cells (2 x 10(5) cells) for 2 days in a serum free media and 5 alpha R activity was measured by the %-conversion of tracer [3H]-testosterone to dihydrotestosterone (DHT) over a 4-h period. Activin significantly stimulated 5 alpha R activity in a dose related manner (control 3.0 +/- 0.4%, activin (1.2 x 10(-9) M) 6 +/- 0.7%, P < 0.01, (2.4 x 10(-9) M) 8.5 +/- 0.6%, P < 0.001). In comparison, androgen (DHT 10(-7) M) induction of 5 alpha R was 4.7 +/- 0.2%, P < 0.05. Combined exposure of fibroblasts to activin (1.2 x 10(-9) M) and androgen (10(-7) M) did not result in additive or synergistic effect on 5 alpha R activity. In contrast, exposure of cells to an androgen (10(-7) M) and TGF-beta (2 x 10(-10) M) led to synergistic effects on 5 alpha R activity (control 1.5 +/- 0.1%, DHT 2.6 +/- 0.2% TGF-beta 1 4.8 +/- 0.5, TGF-beta 1 + DHT 9.2 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1995 Jan
PMID:Activin and inhibin have opposite effects on steroid 5 alpha-reductase activity in genital skin fibroblasts. 779 40

Xenopus in vitro studies have implicated both transforming growth factor beta (TGF-beta) and fibroblast growth factor (FGF) families in mesoderm induction. Although members of both families are present during mouse mesoderm formation, there is little evidence for their functional role in mesoderm induction. We show that mouse embryonic stem cells, which resemble primitive ectoderm, can differentiate to mesoderm in vitro in a chemically defined medium (CDM) in the absence of fetal bovine serum. In CDM, this differentiation is responsive to TGF-beta family members in a concentration-dependent manner, with activin A mediating the formation of dorsoanterior-like mesoderm and bone morphogenetic protein 4 mediating the formation of ventral mesoderm, including hematopoietic precursors. These effects are not observed in CDM alone or when TGF-beta 1, -beta 2, or -beta 3, acid FGF, or basic FGF is added individually to CDM. In vivo, at day 6.5 of mouse development, activin beta A RNA is detectable in the decidua and bone morphogenetic protein 4 RNA is detectable in the egg cylinder. Together, our data strongly implicate the TGF-beta family in mammalian mesoderm development and hematopoietic cell formation.
Mol Cell Biol 1995 Jan
PMID:Evidence for involvement of activin A and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development. 779 20

Inhibin-alpha-deficient mutant mice have been generated by a targeted deletion of the inhibin-alpha gene through homologous recombination in murine embryonic stem cells. Essentially all of the homozygous mutants develop gonadal sex cord-stromal tumors. To investigate their endocrine and proliferative characteristics, gonadal tumor cells were maintained in vitro. Cells from inhibin-alpha-deficient mice multiplied poorly; however, cells from mice deficient in both inhibin-alpha and p53 proliferated rapidly and showed higher saturation density and plating efficiency, thus allowing the establishment of clonal tumor cell lines. Although negligible estrogen and testosterone was produced by the clonal cells, high levels of progesterone were secreted. A clonal testis tumor cell line (inhibin-alpha/p53 deficient) showed no response to exogenous FSH, human CG (hCG), or inhibin A but exhibited a 6- to 8-fold increase in progesterone production in response to forskolin treatment. The stimulatory effect of forskolin was, however, partially blocked by activin treatment. Northern blot analysis revealed inhibin beta A and beta B mRNA expression in these cells. Furthermore, Western blot analyses indicated the secretion of the beta A-subunit protein. We further tested the role of activin on tumor cell growth. Treatment with follistatin, an activin-binding protein, inhibited tumor cell replication in a dose-dependent manner. In contrast, treatment with activin A stimulated tumor cell growth by itself and partially blocked follistatin action. Incorporation of thymidine into DNA of these cells was also stimulated by activin. In addition, treatment with antiactivin A serum inhibited tumor cell replication and blocked the stimulatory action of activin on cell growth. The activin action is likely mediated by specific receptors because cross-linking of [125]activin to the 50-55 kilodalton type I and 75-80 kilodalton type II receptors was found using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Northern blot analysis also revealed follistatin mRNA expression in the tumor cells, suggesting these cells are related to granulosa cells. Our findings indicate that activin can act as an autocrine growth factor in stimulating the proliferation of gonadal tumor cell lines derived from inhibin-alpha and p53-deficient mice and inhibits progesterone production. These tumor cell lines are useful for studies on the regulation of gonadal cell proliferation and steroidogenesis as well as the signaling pathway mediating activin action.
Mol Endocrinol 1994 Aug
PMID:Characterization of gonadal sex cord-stromal tumor cell lines from inhibin-alpha and p53-deficient mice: the role of activin as an autocrine growth factor. 799 39

Site-directed mutagenesis and mammalian cell expression was used to analyze the function of each of the 13 cysteine residues in the human activin A beta-subunit precursor. Substitution of the four cysteine residues in the proregion with alanine residues did not affect the function of the proregion in facilitating the dimerization and secretion of activin A homodimers. A series of activin mutants were constructed in which the nine cysteine residues (amino acids 4, 11, 12, 40, 44, 80, 81, 113, and 115) in the mature 116-amino acid beta-subunit were individually altered to alanine residues. Alanine substitution at either cysteine residues 4 or 12 did not interfere with homodimer formation, but the mutant activin A molecules had reduced biological and receptor binding activity (2- to 3-fold). Activin A monomers were produced when cysteine mutants 44, 80, and 113 were expressed in tissue culture cells. Monomers of cys mutants 44 and 80 had approximately 2% of the biological and receptor binding activity of wild type activin A. Cys 113 monomers had undetectable levels of biological activity. No detectable activin monomers or dimers were secreted from cells transfected with plasmids containing cys mutants 11, 40, 81, and 115. The data presented here suggest that a low level of noncovalent dimer formation of cysteine mutant monomers 44 and 80 may explain their low level of biological activity. Therefore, dimer formation is suggested to be an essential prerequisite for high affinity receptor binding and biological potency.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1994 Mar
PMID:Functional analysis of the cysteine residues of activin A. 801 50

Activins, the dimeric polypeptides of inhibin beta-subunits, exhibit paracrine effects on cell proliferation, differentiation, and various other cell functions. The complex biological response to activin appears to involve multiple receptors. In the present study, we examined the isoform mRNA expression of both activin receptor type II (ActR-II) and type IIB (ActR-IIB) genes in mouse reproductive organs, cumulus-oocyte complexes (COCs), and ovulated oocytes. Northern blot analyses of female and male reproductive organs with single-stranded ActR-II cDNA probes revealed that mouse ovaries expressed high levels of the 6.0 kilobase (kb) mRNA, whereas the 3.0 kb transcript was the major mRNA species found in the testis. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that both COCs and oocytes contained ActR-II mRNA. To examine the expression of ActR-IIB gene, primer selection was made outside the two alternative splicing sites in order to amplify the cDNAs of all four distinct receptor isoforms. The results of RT-PCR demonstrated that isoforms IIB2 and IIB4 were the major mRNA species expressed in both female and male gonads and extragonal reproductive tissues. The ovary expressed all four mRNA isoforms, whereas the testes expressed only three isoforms. whereas the testes expressed only three isoforms. Furthermore, COCs and oocytes contained only the ActR-IIB2 isoform. The differential expression of both activin receptor mRNA isoforms in the reproductive organs suggests that distinct alternative splicing mechanisms are involved in activin receptor gene expression in male and female gonads, and that each of the activin receptors may have its own biological function in reproduction.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1994 May
PMID:Expression of activin receptor II and IIB mRNA isoforms in mouse reproductive organs and oocytes. 804 70

The inhibin-related peptides are present in the testis from early gestation through adulthood. They are produced from multiple testicular sites in a highly regulated manner, suggesting important paracrine roles. Similarly, receptors for these peptides are located in specific stages of the seminiferous tubule and on particular cell types, and an additional level of control is afforded by specific binding proteins, such as follistatin, which may regulate bioavailability. The actions of these factors include the modulation of interstitial cell function and the increase of spermatogonial proliferation in vitro. It thus appears that activin and inhibin are significant factors in the local control of testicular function.
Mol Cell Endocrinol 1994 Apr
PMID:Inhibins, activins, their binding proteins and receptors: interactions underlying paracrine activity in the testis. 805 63

The sites of follistatin and alpha and beta A inhibin gene expression were examined by in situ hybridization in sheep ovaries during the early and mid-luteal phases (days 3 and 10) of the oestrous cycle and a prostaglandin F2 alpha (PGF 2 alpha)-induced follicular phase. Follistatin mRNA was detected in the granulosa cells of preantral, antral and early atretic follicles at all stages of the oestrous cycle, and in the corpora lutea at the early and mid-luteal stages of the cycle. However, only low levels of expression of follistatin were observed in the presumptive preovulatory follicle at 56 h after treatment with PGF 2 alpha. Both alpha and beta A inhibin were shown to be expressed in ovaries at all stages of the oestrous cycle. In situ hybridization localized alpha subunit mRNA to the granulosa cells of most, but not all, healthy antral follicles, and to no other ovarian cell type. In contrast, expression of the beta A subunit was confined to a few medium-to-large healthy antral follicles. In antral follicles expressing beta A inhibin, mRNAs for alpha inhibin and follistatin were always detected, but the converse was not true. Unlike follistatin, no alpha and beta A inhibin expression was seen in preantral follicles, developing corpora lutea, or follicles undergoing atresia. These results show that, in the adult sheep ovary, follistatin gene expression is a constitutive event in all growing follicles from the early preantral stage, and also provide indirect evidence of the involvement of follistatin, but not inhibin or activin, in the early stages of ovarian follicle development in sheep.
J Mol Endocrinol 1994 Apr
PMID:Localization of ovine follistatin and alpha and beta A inhibin mRNA in the sheep ovary during the oestrous cycle. 806 Apr 83

The bone morphogenetic proteins (BMPs) are a group of transforming growth factor beta (TGF-beta)-related factors whose only receptor identified to date is the product of the daf-4 gene from Caenorhabditis elegans. Mouse embryonic NIH 3T3 fibroblasts display high-affinity 125I-BMP-4 binding sites. Binding assays are not possible with the isoform 125I-BMP-2 unless the positively charged N-terminal sequence is removed to create a modified BMP-2, 125I-DR-BMP-2. Cross-competition experiments reveal that BMP-2 and BMP-4 interact with the same binding sites. Affinity cross-linking assays show that both BMPs interact with cell surface proteins corresponding in size to the type I (57- to 62-kDa) and type II (75- to 82-kDa) receptor components for TGF-beta and activin. Using a PCR approach, we have cloned a cDNA from NIH 3T3 cells which encodes a novel member of the transmembrane serine/threonine kinase family most closely resembling the cloned type I receptors for TGF-beta and activin. Transient expression of this receptor in COS-7 cells leads to an increase in specific 125I-BMP-4 binding and the appearance of a major affinity-labeled product of approximately 64 kDa that can be labeled by either tracer. This receptor has been named BRK-1 in recognition of its ability to bind BMP-2 and BMP-4 and its receptor kinase structure. Although BRK-1 does not require cotransfection of a type II receptor in order to bind ligand in COS cells, complex formation between BRK-1 and the BMP type II receptor DAF-4 can be demonstrated when the two receptors are coexpressed, affinity labeled, and immunoprecipitated with antibodies to either receptor subunit. We conclude that BRK-1 is a putative BMP type I receptor capable of interacting with a known type II receptor for BMPs.
Mol Cell Biol 1994 Sep
PMID:Characterization and cloning of a receptor for BMP-2 and BMP-4 from NIH 3T3 cells. 806 29


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