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)

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

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

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

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

Activin, a member of the transforming growth factor-beta superfamily, has been shown to be a critical regulator in exocrine and endocrine pancreas formation. The purpose of our study was to describe the ontogeny of activin B and its inhibitor, follistatin, in developing pancreas and to elucidate potential mechanisms for exocrine and endocrine lineage selection. Mouse embryonic pancreata were dissected at various ages (day 10 [E10.5] to birth [E18.5]), sectioned, and immunostained for activin B (one of two existing isomers, A and B), follistatin, insulin, and glucagon. In addition, reverse transcriptase-polymerase chain reaction was employed to determine the messenger RNA expression of follistatin in isolated pancreatic epithelia and mesenchyme of various ages. Activin B was first detected at E12.5 in epithelial cells coexpressing glucagon. At E16.5 these coexpressors appeared as clusters in close proximity to early ducts. By E18.5 activin B was localized to forming islets where cells coexpressed glucagon and were arranged in the mantle formation characteristic of mature alpha cells. Follistatin was found to be ubiquitous in pancreatic mesenchyme at early ages by immunohistochemical analysis, disappearing sometime after E12.5. Follistatin reappeared in E18.5 islets and remains expressed in adult islets. Follistatin messenger RNA was first detected in epithelium at E11.5, preceding its protein expression in islets later in gestation. We propose that mesenchyme-derived follistatin inhibits epithelium-derived activin at early embryonic ages allowing for unopposed exocrine differentiation and relative suppression of endocrine differentiation. At later ages the decrease in the amount of mesenchyme relative to epithelium and the subsequent drop in follistatin levels liberates epithelial activin to allow differentiation of endocrine cells to form mature islets by the time of birth.
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PMID:Ontogeny of activin B and follistatin in developing embryonic mouse pancreas: implications for lineage selection. 1076 89

The expression of mRNAs for transforming growth factors (TGF-beta2, myostatin, activin-B, and follistatin), insulin-like growth factors (IGF-I and -II), and fibroblast growth factor (basic, bFGF) was investigated in satellite cells derived from chicken pectoralis major (PM) and biceps femoris (BF) muscles in the stages from initiation of proliferation to fusion. These growth factor gene cDNAs were synthesized by reverse transcriptase polymerase chain reaction (RT-PCR). No myostatin, activin-B, follistatin or bFGF expression was detected in either cell culture at 0 h. TGF-beta2 mRNA level increased at 48 h (P < 0.01) and remained constant through 144 h in both PM and BF satellite cell cultures. The ontogeny of myostatin gene expression with the exception of a sharp increase in BF culture at 72 h (P < 0.01), was nearly identical in both cell cultures. Activin-B mRNA level in PM satellite cells was higher than that in BF satellite cells at 72 h and 120 h (P < 0.01). Follistatin mRNA in PM satellite cells was higher than that in BF satellite cells at 24, 96, and 120 h culture (P < 0.01). No IGF-I gene expression was detected in cell cultures at any time point. IGF-II gene expression in BF satellite cells declined at 96 h (P < 0.01) and remained reduced until 144 h. bFGF mRNA in both satellite cell cultures increased at 24 h (P < 0.05) and remained at this level in BF satellite cells through 144 h.
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PMID:Temporal expression of growth factor genes during myogenesis of satellite cells derived from the biceps femoris and pectoralis major muscles of the chicken. 1114 9

Ovarian surface epithelium (OSE) is the tissue of origin for the majority of ovarian cancers. The mechanism underlying the neoplastic transformation of OSE to ovarian cancer is poorly understood. Activin, a member of the transforming growth factor-beta superfamily, has been shown to increase cell proliferation in ovarian cancer cells. The present study was carried out to investigate the expression and regulation of activin/inhibin subunits and activin receptors in normal and neoplastic OSE. Using reverse transcriptase-polymerase chain reaction and Southern blot analysis, the mRNA levels of alpha, betaA and betaB subunits and activin receptor type IIA and IIB were analyzed in normal OSE and the ovarian cancer cell line, OVCAR-3 cells. The alpha and betaA subunits were highly expressed in normal OSE when compared to OVCAR-3 cells. By contrast, betaB subunit was highly expressed in OVCAR-3 cells, when compared to normal OSE cells. Interestingly, activin receptor IIB mRNA levels were significantly higher in OVCAR-3 when compared to normal OSE cells, whereas activin receptor IIA mRNA levels were the same in both cell types. To characterize the growth modulatory role of activin during neoplastic progression, normal OSE and OVCAR-3 cells were treated with recombinant human activin A (rh-activin A). At concentrations of 1,10 and 100 ng/ml, rh-activin A stimulated the growth of OVCAR-3 cells, but not of normal OSE. Treatment with follistatin, binding protein of activin, attenuates the stimulatory effect of activin. To determine whether the growth stimulatory action of activin in the neoplastic OSE is mediated via an autocrine regulatory mechanism, OVCAR-3 cells were treated with rh-activin A in a dose- and time-dependent manner and the expression levels of activin/inhibin subunits and activin receptors were investigated. Treatments with activin increased the alpha and betaA subunit mRNA levels in a dose- and time-dependent manner. However, no difference was observed in levels of betaB subunit, or in activin receptor type IIA and IIB mRNAs following activin treatments in OVCAR-3 cells. Taken together, these results suggest that different levels of activin/inhibin and activin receptor isoforms are expressed in normal and neoplastic OSE cells. In addition, the altered expression of the activin/inhibin subunits, as well as the cell proliferative effect of activin observed in OVCAR-3 but not in normal OSE cells, indicate that activin may act as an autocrine regulator of neoplastic OSE progression.
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PMID:Differential expression of activin/inhibin subunit and activin receptor mRNAs in normal and neoplastic ovarian surface epithelium (OSE). 1130 76

Peroxisome proliferators stimulate hepatocyte growth in rat liver in vivo. Activin A, a homodimer of inhibin betaA, inhibits DNA synthesis in hepatocytes. The inhibitory action of activin A is suppressed by follistatin, an activin-binding protein. In this paper, we investigated whether administration of di-n-butyl phthalate (DBP), a peroxisome proliferator, modifies the production of activin A and follistatin in rat liver by hourly monitoring of inhibin betaA and follistatin mRNA levels by reverse transcriptase polymerase chain reaction analysis. The mRNA levels of the other inhibin beta chains (inhibin betaB and betaC) were examined in a similar manner. The inhibin betaA mRNA level decreased to about 30% by 3 h after DBP administration (8.6 mmol/kg body weight), remained low until 12 h, and returned to its original level by 24 h. The follistatin mRNA level increased to about 2 times by 6 h, and returned to its original level by 24 h. The inhibin betaB mRNA had started to increase by 1 h, peaked at 6 h at about 4 times its initial level, and returned to its original level by 12 h. The inhibin betaC mRNA level had doubled by 6 h and it returned to its original level. These results indicate that the growth stimulatory action of peroxisome proliferators may be mediated via the decrease in activin A level and activity and suggest that the increases in follistatin as well as inhibin betaB and betaC chains may play a role in peroxisome proliferator-stimulated hepatocyte growth.
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PMID:Regulation of inhibin beta chains and follistatin mRNA levels during rat hepatocyte growth induced by the peroxisome proliferator di-n-butyl phthalate. 1223 Jan 21

Activin A (beta A beta A) and inhibin A (alpha beta A) are dimeric glycoproteins secreted from early to term pregnancy in the maternal circulation. They circulate in higher amounts in women with gestational hypertension and/or pre-eclampsia, the most important gestational diseases also causing fetal growth restriction (FGR). Since no data are available in patients with pre-eclampsia and superimposed FGR, by using two-site immunoassays we evaluated serum activin A and inhibin A levels in serum samples collected from: healthy normotensive pregnant controls (n = 42); and women with pre-eclampsia with (n = 19) or without superimposed FGR (n = 21). In addition, by quantitative reverse transcriptase-polymerase chain reaction the changes of alpha- and beta A-subunit mRNA expression in placentas collected from healthy controls (n = 7) and pre-eclamptic pregnancies with (n = 6) or without (n = 6) superimposed FGR was also investigated. Activin A and inhibin A serum levels were significantly higher in pre-eclampsia, and the presence of FGR did not significantly modify these concentrations. Similarly, inhibin-subunit mRNA levels in placentas from pre-eclampsia were significantly higher than in controls, and FGR did not significantly affect this expression. The present data suggest that the increased placental expression of inhibin subunit mRNAs is part of the mechanism leading to increased serum activin A and inhibin A levels.
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PMID:Pre-eclampsia with fetal growth restriction: placental and serum activin A and inhibin A levels. 1258 30


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