Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GH3 pituitary tumor cells have surface receptors for transforming growth factors-beta (TGF-beta s) and activins/inhibins. GH3 cell mRNA was screened by a novel reverse transcriptase-polymerase chain reaction technique with primers for receptor serine-threonine kinases. We isolated rat homologs of previously identified clones for type I (ALK-2 and ALK-5) and type II (ActRII, TGF-beta RII) activin and TGF-beta receptors, together with a novel clone, whose full-length version was isolated from a GH3 cell cDNA library. Named B1, it encodes a 505-amino-acid protein belonging to the family of type I receptor serine/threonine kinases. The kinase domain of B1 exhibits 90% identity to that of the TGF-beta type I receptor. B1 mRNA is expressed not only in pituitary cells but also in all other cells and tissues examined. B1 protein can be expressed on the cell surface, but cannot bind ligand unless a type II receptor is also present. When coexpressed with the type II receptors specific for TGF-beta or activin, B1 can be efficiently cross-linked to either ligand, suggesting that it can form heteromeric complexes with both type II receptor subunits.
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PMID:Molecular characterization of a type I serine-threonine kinase receptor for TGF-beta and activin in the rat pituitary tumor cell line GH3. 781 22

Specific factors involved in the pathogenesis of tumors that stimulate clonal human pituitary adenoma cell proliferation remain unknown. An important question regarding the pathogenesis of human pituitary tumors is whether they synthesize autocrine regulatory factors that regulate both hormone biosynthesis and neoplastic growth. Activin and inhibin are both comprised of inhibin subunits and have diverse regulatory roles as growth and differentiation factors in normal and neoplastic tissue. Activin stimulates FSH beta messenger ribonucleic acid (mRNA) biosynthesis and FSH secretion, and these effects are down-regulated in normal gonadotrophs by the endogenous glycoprotein follistatin. In addition to its effects on gonadotrophs, activin modulates hormone secretion by somatotroph and corticotroph cell lines. It is not known whether human neoplastic pituitary tissue synthesizes inhibin subunits or follistatin or whether their expression is cell type specific. We investigated whether alpha-, beta A-, and beta B-inhibin subunit and follistatin mRNAs could be detected in 27 human pituitary adenomas [clinically nonfunctioning (n = 11), somatotroph (n = 5), corticotroph (n = 5), and lactotroph (n = 6)] using reverse transcriptase-polymerase chain reaction techniques. Twenty-six of the tumors contained mRNAs encoding one or more inhibin subunits. beta B-Inhibin mRNA was the most prevalent (81% of tumors), followed by beta A-inhibin (59% of tumors) and alpha-inhibin (52% of tumors). Endogenous alpha-, beta A-, and beta B-inhibin subunit mRNA synthesis was also examined in normal human pituitary and testicular complementary DNA libraries, and all subunit mRNAs were detected. In contrast to the widespread expression of inhibin subunits in pituitary tumors, follistatin mRNA was detected in a subset of nonfunctioning tumors (54%) as well as in control normal human pituitary and testicular complementary DNA libraries. Tumor-specific follistatin biosynthesis was not observed in other pituitary tumor subtypes. These data are the first to demonstrate that 1) endogenous inhibin subunits are synthesized in human pituitary adenomas of all known secretory phenotypes as well as normal pituitary tissue; and 2) follistatin gene expression in pituitary adenomas is specific to clinically nonfunctioning or gonadotropin subunit-producing tumors. The characterization of inhibin subunit and follistatin biosynthesis by human pituitary tumors will be important in investigating their potential roles in regulating both tumor phenotype and cell proliferation.
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PMID:Human pituitary adenomas express endogenous inhibin subunit and follistatin messenger ribonucleic acids. 782 3

As an initial step in determining whether activin could play a role in the development of gonadotroph adenomas, we attempted to determine if activin/inhibin subunit messenger ribonucleic acids (mRNAs) are expressed by these pituitary tumors. We selected 19 pituitary adenomas that had been excised by transsphenoidal surgery and determined by immunocytochemical criteria to be gonadotroph adenomas. Total RNA was extracted from these adenomas and reverse transcribed. The resulting pit-1 complementary DNA, expected to be present only in somatotroph, lactotroph, and thyrotroph cells, was amplified by the polymerase chain reaction to test the possibility that the adenoma tissue was contaminated by normal pituitary tissue. Only the 10 adenomas that did not express pit-1 mRNA were subjected to further analysis by polymerase chain reaction amplification of the adenoma reverse transcriptase products for the activin/inhibin beta B-, beta A-. and alpha-subunits. All 10 adenomas expressed beta B-subunit, none of the 10 expressed the beta A-subunit, and 6 of the 10 expressed the alpha-subunit. We conclude that gonadotroph adenomas express mRNAs for activin/inhibin beta B- and alpha-subunits. The relationship of beta B expression to the pathogenesis of gonadotroph adenomas remains to be determined.
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PMID:Expression of activin/inhibin subunit messenger ribonucleic acids by gonadotroph adenomas. 796 35

We previously reported that follistatin, an activin-binding protein, is produced in arteriosclerotic lesions. Here, the expression of activin-A which promotes the growth of vascular smooth muscle cells was examined in arteriosclerotic lesions of WHHL (Watanabe heritable hyperlipidemic) rabbits. Activin-A mRNA was detected in normal aorta by reverse transcriptase-polymerase chain reaction using specific primers for activin-A cDNA and was increased remarkably in arteriosclerotic lesions. In addition, using the cloned rabbit activin-A cDNA, RNA probe was prepared and in situ hybridization histochemistry was performed. Activin-A transcripts were detected abundantly in neointima of the diseased artery. Furthermore, immunohistochemistry also detected activin-A at the protein level. These observations suggest that activin-A is a cytokine expressed in arteriosclerotic lesions and might be involved in the pathogenesis of atherosclerosis.
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PMID:Demonstration of activin-A in arteriosclerotic lesions. 799 62

Gonadotropin subunit gene expression is regulated by gonadal, hypothalamic, and locally derived hormones. In particular, activin rapidly (within hours) acts at the gonadotrope to selectively increase the expression of FSH beta messenger RNA (mRNA). A family of activin receptors (ActRI, ActRII, and ActRIIB) has been identified, which is expressed in the pituitary as well as numerous other tissues in which activin is thought to act. As alterations in activin sensitivity could modulate activin action and, thereby, FSH beta mRNA, the purpose of this study was to determine whether ovariectomy (OVX), which results in rapid (< 2 h) increases in FSH beta, is associated with changes in ActRII gene expression. Adult female rats were ovariectomized, and some animals also received a GnRH antagonist from the time of OVX. Animals were killed between 2 h and 7 days later, and ActRII mRNA levels were measured by a quantitative reverse transcriptase-polymerase chain reaction assay. Although levels were unchanged at 2 h, ActRII mRNA levels increased 5- to 6-fold by 8 h and remained increased through 7 days after OVX. These changes were not altered by GnRH blockade. To determine whether ActRII was regulated by gonadal steroids, female rats were ovariectomized, and some animals were replaced with estradiol and progesterone (Silastic implants) for 2 days. Again, ActRII mRNA levels increased significantly after OVX, and gonadal steroid replacement had no effect. Finally, to investigate whether pituitary ActRII mRNAs are regulated by circulating inhibin, intact female rats were treated with an inhibin antiserum or nonimmune sheep serum as a control and killed 12 h later. Despite its action to increase FSH beta mRNA and FSH secretion, selective removal of inhibin did not alter ActRII mRNA levels. Based on these results we conclude the following. 1) Pituitary ActRII mRNAs increase rapidly after OVX, although increases in FSH beta precede changes in ActRII. These data suggest that changes in activin sensitivity may be a factor involved in the regulation of FSH beta. 2) An ovarian factor, other than inhibin, estradiol, and progesterone, acting independently of GnRH maintains an inhibitory tone on pituitary ActRII gene expression in adult rats.
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PMID:Ovarian regulation of pituitary inhibin subunit and activin receptor type II gene expression: evidence for a nonsteroidal inhibitory substance. 807 Mar 90

Activin is a potent inducer of axial mesoderm in vitro and may have a similar role in vivo. Xenopus laevis eggs contain significant amounts of activin or activin-like factors, but maternal activin transcripts have not been detected in Xenopus eggs. The maternal activin protein might be translated from activin beta A or beta B mRNAs that are transiently expressed during oogenesis, or activin polypeptides might be transferred from follicle cells to oocytes. To assess these possibilities we studied activin mRNAs in follicle cells and oocytes by reverse transcriptase-polymerase chain reaction (RT-PCR) and RNA blotting. Activin beta A, beta B1, and beta B2 transcripts occur in follicle cells; among them, beta A mRNA is by far the most abundant. Activin beta A and beta B1 mRNAs were not detected by RT-PCR in the corresponding stage IV oocytes, but activin beta B2 transcripts were found at low levels. These observations are consistent with synthesis of activin beta A and possibly beta B polypeptides in follicle cells followed by their secretion and uptake by oocytes, although synthesis of activin beta B2 in the oocytes could make a contribution to the maternal activin pool.
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PMID:Expression of activin transcripts in follicle cells and oocytes of Xenopus laevis. 840 80

Production of a member of transforming growth factor-beta (TGF-beta) superfamily, activin A, was examined in the bone tissue by using reverse transcriptase polymerase reaction. As a result, specific bands were detected showing the presence of activin A mRNA in the bone tissues. In order to localize the production site of activin A in the bone tissues, we tried to immunolocalize activin A in fetal mouse calvaria cultured in a medium containing fetal calf serum, 1 alpha-25(OH)2 vitamin D2 and parathyroid hormone. In these cultured calvaria, bone tissues including bone-resorbing osteoclasts in vitro were observed. Positive staining demonstrating the presence of activin A resided inside of the multinucleated cells in the bone resorbing lacunae, suggesting the production of activin A in osteoclasts. Activin A was also localized immunohistochemically in the osteoclast-like multinucleated cells developed in vitro. These results suggest that osteoclast produce activin in the bone tissues and that activin may play some roles by autocrine and/or paracrine manner in bone metabolisms.
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PMID:Immunohistochemical detection of activin A in osteoclasts. 896 19

Expression of the follistatin (FS) and inhibin/activin (I/A) alpha, beta(A), and beta(B) subunit genes in porcine ovarian follicles was evaluated by reverse transcriptase polymerase chain reaction and/or RNase protection procedures to establish changes during the final stages of follicular development. For the I/A alpha and beta(A) subunits, expression increased (p < 0.05) as follicles progressed to the mid-stage of the follicular phase. The beta(B) subunit was expressed in lower concentrations, and all three I/A subunits showed a marked reduction (p < 0.01) in expression by the late stage of follicular development. In contrast to this pattern, FS gene expression decreased (p < 0.05) as follicles developed from the early (low estradiol) to the mid stage (high estradiol) and continued to decline in advanced follicles (after estrus). The predominant mRNA encoded for FS-315, and the ratio of mRNA for FS-315 to mRNA for FS-288 did not differ significantly during the three stages. Within an animal, concentration of FS mRNAs was related more to stage of the follicular phase than to follicular size. Follicular fluid concentration of FS changed in a manner similar to that observed for expression of its gene. We conclude that expression of the FS gene and translation of its mRNA decrease as follicles approach ovulatory status.
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PMID:Expression of follistatin and inhibin/activin subunit genes in porcine follicles. 920 88

The aim of the present study was to evaluate whether spontaneous labor at term and pathological preterm labor are associated with changes in the expression of activin A and activin receptor mRNAs in fetal membranes. In addition, amniotic fluid activin A concentration in women delivering at term or undergoing preterm labor was also measured. The expression of activin beta A subunit and activin receptor type II and type IIB mRNAs was assessed by reverse transcriptase-PCR on specimens of amnion and chorion collected from patients delivering at term or undergoing preterm labor. Control specimens were collected from women delivered by elective cesarean section who had not experienced labor. A specific two-site ELISA was used to measure activin A concentrations in the amniotic fluid. A cross-sectional study of amniotic fluid retrieved by amniocentesis from 109 pregnant women was carried out. Patients were classified into the following groups: (1) healthy controls at term but not in labor (n = 25); (2) healthy controls at term in spontaneous labor (n = 40); (3) healthy controls between 23 and 36 weeks of gestation (n = 12); (4) patients in preterm labor responding to tocolytic treatment (n = 19); (5) patients in preterm labor with subsequent delivery (n = 13). Activin beta A subunit and activin receptor type IIB mRNA levels in both the chorion and amnion in women delivering at term or after preterm labor were significantly higher than in women delivering without undergoing labor (P < 0.01). Expression of activin receptor type II mRNA in membranes did not differ among the three groups of women. Amniotic fluid activin A concentration in patients in labor was significantly higher than in those at term but not in labor (P < 0.01). Patients in preterm labor had significantly higher amniotic fluid activin A concentrations than women at the same stage of gestation (P < 0.01). The highest values were found in women undergoing preterm labor and subsequent delivery. In conclusion, spontaneous labor and preterm labor are characterized by increased synthesis and release of activin A from amniotic and chorionic cells and by an augmented expression of activin type IIB receptor.
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PMID:High levels of fetal membrane activin beta A and activin receptor IIB mRNAs and augmented concentration of amniotic fluid activin A in women in term or preterm labor. 924 42

Transforming growth factor (TGF)-beta superfamily members and their receptors play a part in the differentiation of pulp cells into odontoblasts during reparative dentinogenesis. Bovine primary pulp-cell culture has been used as an in vitro model for proliferation and differentiation of pulp cells into preodontoblasts. To explore the molecular cascade of odontoblast differentiation, Northern blot analyses and reverse transcriptase polymerase chain reaction were here used to investigate the expression patterns of the genes for TGF-beta superfamily members: TGF-beta 1, namely bone morphogenetic protein (BMP)-4, BMP-7, activin-beta A and activin-beta B, and their type I and type II receptors, namely activin receptor-like kinase (ALK)-2 (ActR-I), ALK-3 (BMPR-IA), ALK-4 (ActR-IB), ALK-5 (T beta R-I), BMPR-II and T beta R-II, during differentiation of pulp cells into preodontoblasts in bovine adult pulp-cell culture. TGF-beta 1 and BMP-4 mRNAs were expressed from day 14 when matrix formation increased. BMP-7 mRNA was expressed only on day 28 when osteocalcin appeared. ALK-2 mRNA was increased from the beginning of the culture. ALK-3 and ALK-5 mRNAs first decreased on day 14 and increased again on day 21. T beta R-II and BMPR-II mRNAs were almost constant. These results suggest that the differentiation of pulp cells into preodontoblasts may be regulated by changes in the temporally coordinated expression pattern of TGF-beta superfamily members and their receptors, including up-regulation of transcription of TGF-beta 1, BMP-4, BMP-7, ALK-2, ALK-3, and ALK-5.
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PMID:Temporal changes in expression of transforming growth factor-beta superfamily members and their receptors during bovine preodontoblast differentiation in vitro. 929 67


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