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H Seo

Publications and source records attributed to H Seo.

At least 19 recordsLinked to original sources
PubMed1999

9-cis-retinoic acid decreases the level of its cognate receptor, retinoid X receptor, through acceleration of the turnover.

In this study, we investigated the ligand-mediated regulation of retinoid X receptor (RXR) in two human cell lines (HepG2 and JEG-3 cells), which have been reported to express RXRalpha predominantly. Western blot analysis revealed that a treatment with 1 microM 9-cis-retinoic acid (9-cis RA) for 24 h decreased RXRalpha protein level to 72 +/- 9 and 75 +/- 7% in HepG2 and JEG-3 cells, respectively, when the levels in the non-treated cells were expressed as 100%. The decrease was not due to the changes in steady-state level of RXRalpha mRNA or its stability as revealed by Northern blot analysis. However, the 9-cis RA treatment decreased the half-life of RXRalpha protein as determined by pulse-chase analysis. It was thus demonstrated that 9-cis RA downregulates RXRalpha by increasing the turnover of the protein in the two cell lines. The ligand-dependent downregulation of RXRalpha protein may be important for several hormonal signalings, in which the receptors heterodimerize with RXR.

Alitretinoin↗
PubMed1999

A DNA unwinding factor involved in DNA replication in cell-free extracts of Xenopus eggs.

BACKGROUND: Alteration of chromatin structure is a key step in various aspects of DNA metabolism. DNA unwinding factors such as the high mobility group (HMG) proteins are thought to play a general role in controlling chromatin structure and a specific role in controlling DNA replication. For instance, in the in vitro simian virus 40 replication system, minichromosomes containing HMG-17 replicate more efficiently than those without it, suggesting that HMG-17 enhances the rate of replication of a chromatin template by unfolding the higher-order chromatin structure. At present, however, only limited data suggest an involvement of DNA unwinding factors in DNA replication. RESULTS: We purified from Xenopus eggs a novel heterodimeric factor, termed DNA unwinding factor (DUF), that consists of 87 kDa and 140 kDa polypeptides. DUF unwinds closed-circular duplex DNA in the presence of topoisomerase I, but it does not possess a DNA gyrase activity: it does not introduce negative supercoils into DNA at the expense of ATP hydrolysis. Cloning and sequencing of the cDNAs encoding the two polypeptides revealed that the 87 kDa polypeptide is homologous to a mammalian HMG protein, T160/structure-specific recognition protein. The 140 kDa polypeptide is homologous to yeast Cdc68, a protein that controls the expression of several genes during the G1 phase of the cell cycle by modulating chromatin structure. Immunodepletion of DUF from Xenopus egg extracts drastically reduced the ability of the extract to replicate exogenously added sperm chromatin or plasmid DNA. CONCLUSIONS: We propose that DUF plays a role in DNA replication in Xenopus egg extracts.

Amino Acid Sequence↗
PubMed1999

Cleavage of RXRalpha by a lysosomal enzyme, cathepsin L-type protease.

In this study, we characterized a protease responsible for the cleavage of RXRalpha in two human derived cell lines, HepG2 and JEG-3 cells. Electrophoretic mobility shift assay (EMSA) combined with antibody supershift analysis suggested that contamination of cytoplasmic components during nuclear extract preparation could result in complete cleavage of RXRalpha at its N-terminus in JEG-3 cells, while such proteolytic activity was much less evident in HepG2. When the nuclei were purified in the presence of leupeptin, only full-length RXRalpha was found in the extracts prepared from both JEG-3 and HepG2 cells, suggesting a member of cysteine protease family is responsible for the cleavage. The presence of the protease in the cytoplasm, but not in the nucleus, was confirmed by incubating full-length 35S-labeled RXRalpha with each fraction. The cytoplasmic fraction from JEG-3 and HepG2 cells cleaved RXRalpha into smaller sizes with molecular mass of 45, 43, and 31 kD. Immunoprecipitation with antibodies recognizing distinct epitopes indicated that the cleaved RXRalpha with the size of 45 and 43 kD were truncated at N-terminus in which most of the A/B domain was absent. Using a series of protease inhibitors, the enzyme cleaving RXRalpha was characterized as cathepsin L-type protease. The enzyme activity in JEG-3 cells was much higher than that in HepG2 cells. This is the first demonstration that RXRalpha is cleaved by a lysosomal enzyme, cathepsin L-type protease.

Cathepsin L↗
PubMed1999

Inhibition of growth hormone (GH) secretion by a mutant GH-I gene product in neuroendocrine cells containing secretory granules: an implication for isolated GH deficiency inherited in an autosomal dominant manner.

Isolated GH deficiency (IGHD) type II is a disease inherited in an autosomal dominant manner. Although point mutations at the donor splice site of intron 3 of the GH-I gene have been identified in patients, the mechanism of how such mutations result in severe GH deficiency is unclear. Recently, we identified two mutations in Japanese patients with IGHD type II, G to A substitutions at the first (mutA) and fifth (mutE) nucleotides of intron 3. Messenger ribonucleic acids skipping exon 3 were transcribed from both mutant GH-I genes. We studied in this report the synthesis and secretion of GH encoded by the mutant GH-I genes and tested whether inhibition of wild-type GH secretion by mutant products could be demonstrated in cultured cell lines. A metabolic labeling study in COS-1 cells revealed that a mutant GH with a reduced molecular mass was synthesized from the mutant messenger ribonucleic acid and retained in the cells for at least 6 h. On the other hand, the wild-type GH was rapidly secreted into the medium. Coexpression of mutant and wild-type GH did not result in any inhibition of wild-type GH secretion in COS-1 or HepG2 cells. However, coexpression of mutant GH resulted in significant inhibition of wild-type GH secretion in somatotroph-derived MtT/S cells as well as in adrenocorticotroph-derived AtT-20 cells, without affecting cell viability. We conclude that the dominant negative effect of mutant GH on the secretion of wild-type GH is at least in part responsible for the pathogenesis of IGHD type II. Our results also suggest that neuroendocrine cell type-specific mechanisms, including intracellular storage of the secretory proteins, are involved in the inhibition.

Animals↗
PubMed1999

Determinants of exercise-induced ST-segment displacement in the aVL lead in patients with known or suspected coronary artery disease.

Although the aVL lead in exercise electrocardiography is reported to be helpful in identifying a significant narrowing of the left anterior descending coronary artery (LAD), its role in exercise testing has not been fully evaluated. Accordingly, 821 patients who underwent both standard exercise testing and coronary angiography were evaluated. In patients with aVL lead ST elevation, the incidence of a significant narrowing of the LAD (124/165 vs 348/656; p<0.001) was higher than in those without. Multiple logistic regression analysis revealed that the 2 most important variables that correlated with aVL lead ST elevation were a greater number of leads with ST depression in the inferior leads and a smaller amplitude of R wave in the aVL lead. In contrast, variables correlating with aVL lead ST depression in the majority of cases were a greater number of leads with ST depression in all leads and the presence of inferior lead ST elevation. The results of this study indicate that although aVL lead ST elevation could be a marker for LAD narrowing, more important factors such as inferior lead ST-segment depression and the R-wave amplitude of the aVL lead should be taken into consideration. In contrast, ST depression in the aVL lead mostly represents exercise-induced myocardial ischemia of greater extent and severity.

Adult↗
PubMed1999

Glucocorticoids increase retinoid-X receptor alpha (RXRalpha) expression and enhance thyroid hormone action in primary cultured rat hepatocytes.

We have previously demonstrated that dexamethasone (DEX) enhances the T3-dependent increase in type I 5'-deiodinase (5'DI) mRNA in primary cultured rat hepatocytes grown as spheroids. Here we report that DEX-enhanced T3-responsiveness also occurs in two other T3-regulated hepatic genes, Spot 14 and malic enzyme. This enhancement was inhibited by pretreatment with cycloheximide and the stability of 5'DI and Spot 14 mRNAs was not affected by DEX. We thus hypothesized that a factor(s) that augments T3-responsiveness is induced by DEX. Among the possible candidates examined, retinoid-X receptor alpha (RXRalpha), which is a main heterodimer partner with T3 receptor, appeared to be involved. Whereas DEX increased the amount of RXRalpha mRNA, it did not affect the expression of other possible factors such as steroid receptor coactivator-1 and the binding protein of cAMP response element-binding protein. Northern and Western blot analysis, and electrophoretic mobility shift assay revealed that DEX increased RXRalpha expression at both the mRNA and protein levels. Maximal increase in RXRalpha protein was achieved with the addition of physiological concentrations of DEX (10(-8) M). To test whether the DEX-induced increase in RXRalpha affects ligand-dependent transcriptional activation through other receptors that form heterodimer with RXR, we examined its effect on the retinoic acid (RA)/RA receptor (RAR) system. Indeed, DEX also enhanced the RA-dependent increase in RARbeta mRNA in a cycloheximide-sensitive manner. Increase in the level of RXRalpha in hepatocytes by infection with the RXRalpha-expressing adenovirus resulted in enhancement of the T3-dependent increase in 5'DI mRNA. These results strongly suggest that the DEX-induced augmentation of T3-responsiveness in cultured hepatocytes is mediated, in part, by the increased expression of RXRalpha.

Animals↗
PubMed1999

Virilizing adrenocortical adenoma: in vitro steroidogenesis, immunohistochemical studies of steroidogenic enzymes, and gene expression of corticotropin receptor.

BACKGROUND: No reports have yet precisely determined corticotropin (ACTH) responsiveness in virilizing adrenocortical adenoma. METHODS: Five women with an androgen-secreting adrenal adenoma were reviewed. Three of them were examined by in vitro steroidogenesis. Two of these 3 patients were studied by immunohistochemistry of steroidogenic enzymes and for the gene expression of ACTH receptor by Northern blot analysis. RESULTS: In preoperative hormonal determinations plasma and urine androgens had increased. Dexamethasone did not suppress plasma and urinary androgens, nor did ACTH increase them. In vitro steroidogenesis revealed that the adenoma cells produced mainly dehydroepiandrosterone and a small amount of testosterone. ACTH did not increase the in vitro production of androgens. In immunohistochemical staining 5 enzymes involved in adrenal steroidogenesis were all expressed, especially 17 alpha-hydroxylase, which was strongly expressed in tumor cells. ACTH receptor messenger RNA was not detected in virilizing tumor tissues, whereas it was expressed in attached adrenal tissues. CONCLUSIONS: The lack of response to ACTH is the result of a deficiency of ACTH receptor expression in the virilizing tumor cells. Androgens were autonomously produced in adrenal adenoma cells without ACTH regulation.

17-alpha-Hydroxypregnenolone↗
PubMed1999

[A case of traumatic dissecting aneurysm of the C1-2 portion of the internal carotid artery].

The authors report a case of traumatic dissecting aneurysm of the C1-2 portion of the internal carotid artery (ICA) in a 54-year-old woman. She suffered from traumatic SAH due to closed head trauma as a result of a motor vehicle accident. Twenty-five days after this accident, traumatic dissecting aneurysm of the C1-2 portion of the ICA that was caused by closed head trauma was ruptured and increased in size, as revealed by serial angiographic studies. In intraoperative finding, dissection involved the entire circumference of the C1-2 portion of the ICA. Clipping procedures were impossible, so internal carotid ligation and STA-MCA anastomosis was performed. To our knowledge, this traumatic dissecting aneurysm of the C1-2 portion of the ICA was the first case that presented with SAH. We discussed the mechanism of dissection of the ICA and operative strategy suitable for this aneurysm.

Aortic Dissection↗
PubMed1998

Intracellular proteolytic cleavage of 9-cis-retinoic acid receptor alpha by cathepsin L-type protease is a potential mechanism for modulating thyroid hormone action.

We previously reported that the responsiveness of hepatocytes to thyroid hormone is markedly attenuated when they were cultured as monolayers rather than spheroids. To elucidate the mechanisms underlying the altered responsiveness, thyroid hormone receptor auxiliary proteins in the hepatocytes were analyzed by electrophoretic mobility shift assay. The major thyroid hormone receptor auxiliary protein was identified as 9-cis-retinoic acid receptor alpha (RXRalpha) in the hepatocytes regardless of the culture conditions. The cytoplasmic fraction was shown to contain a protease(s) that cleaves RXRalpha at its amino terminus. The presence of the protease in the cytosol, but not in the nucleus, was ascertained by incubating full-length 35S-labeled RXRalpha with each fraction. Using various protease inhibitors, it was shown that cathepsin L-type protease could participate in the cleavage of the RXRalpha. The enzyme activity was much higher in the monolayers than the spheroids. Inhibition of this enzyme activity in the monolayer hepatocyte resulted in the increase of nuclear RXRalpha protein and the augmentation of T3-dependent induction of spot 14 mRNA. These results suggest that the changes in cathepsin L-type protease activity in the cytosol may alter the turnover of RXRalpha in the nucleus and modify the function of steroid receptor superfamilies that heterodimerize with RXRalpha.

Animals↗
PubMed1998

Noradrenergic-specific transcription of the dopamine beta-hydroxylase gene requires synergy of multiple cis-acting elements including at least two Phox2a-binding sites.

Dopamine beta-hydroxylase (DBH) catalyzes the conversion of dopamine to noradrenaline and is selectively expressed in noradrenergic and adrenergic neurons and neuroendocrine cells. Recent data from this laboratory showed that a paired-like homeodomain (HD) protein, Phox2a, interacts with the HD-binding site residing within a composite promoter of the human DBH gene, designated domain IV, in a cell-specific manner and directly controls noradrenergic-specific DBH promoter activity. In this report, we demonstrate that three additional protein-binding sites (i.e., domains I, II, and III) between domain IV and the TATA box are critical for intact DBH promoter activity in noradrenergic cells and that they activate DBH transcription in a highly concerted manner. Transient transfection assays of mutant DBH reporter constructs indicated that domain I was active in every cell line tested, whereas domain III was preferentially active in DBH-positive cells. Remarkably, mutation of domain II was associated with inactivation of DBH promoter activity exclusively in DBH-positive cell lines, defining it as another noradrenergic-specific promoter element. The cell-specific profile of the promoter function of these sequence motifs was further supported by in vitro DNA-binding studies and Southwestern analysis. Furthermore, competition and antibody supershift assays show that transcription factors Sp1 and AP2 are the cognate nuclear factors interacting with domains I and III, respectively. Parallel evidence indicates that domain II is another Phox2a-binding site, demonstrating at least two binding sites for this factor in the upstream DBH promoter. Strikingly, four tandem copies of domain II increased the promoter activity of a minimal DBH promoter by 100- to 200-fold in DBH-positive cell lines without compromising cell specificity. Cotransfection of Phox2a-expression vector dramatically increased the activity of the multiple domain II promoter only in DBH-negative cell lines, confirming that domain II is responsive to Phox2a. Collectively, this study emphasizes a critical role of Phox2a as well as its functional synergism with other transcription factors (e.g., CREB, AP2, and Sp1) in transcriptional activation of the DBH gene.

Animals↗
PubMed1998

Requirement of corepressor binding of thyroid hormone receptor mutants for dominant negative inhibition.

Resistance to thyroid hormone (RTH) is mainly caused by dominant negative inhibition of wild type thyroid hormone receptor (TR) function due to mutations in the ligand binding domain of the TR beta. Because no RTH mutant was identified in the hinge region of the TR, the contribution of this region for dominant negative inhibition was explored. In transient transfection assays, the dominant negative activity of a RTH-type mutant (P453X) was abolished by an introduction of a mutation into the hinge region (P214R). Although this hinge mutation did not alter homo- or heterodimerization with retinoid X receptor (RXR), its association with nuclear receptor corepressor (N-CoR) was impaired. These results indicate that association of corepressor with the RTH mutants through the hinge region is crucial for their dominant negative activity.

Binding Sites↗
PubMed1998

Molecular cloning of sucrase-isomaltase cDNA in the house musk shrew Suncus murinus and identification of a mutation responsible for isolated sucrase deficiency.

Isolated sucrase deficiency has been demonstrated in a line of house musk shrew, Suncus murinus (laboratory name: suncus). This animal belongs to the order Insectivore and is phylogenetically different from ordinarily used laboratory animals. They are believed to have evolved with mainly animal food without sucrose. To study the molecular basis of the sucrase deficiency in suncus, we cloned 6. 0-kilobase (kb) sucrase-isomaltase (SI, EC 3.2.1.48-10) cDNA from suncus intestinal cDNA library. The cDNA clone contained a 5442-base pair (bp)-long open reading frame preceded by an in frame termination codon. The deduced 1813-amino acid sequence showed 68.6, 71.2, and 74.7% similarity with those of rat, rabbit, and human, respectively. A cleavage site between isomaltase and sucrase as well as the region surrounding the catalytic sites for sucrase and isomaltase were conserved among the species. Out of 18 potential N-linked glycosylation sites, 5 were common among all 4 species. In the connecting segment which was enriched with O-linked glycosylation sites in the other species, only two sites were present in suncus. Northern blot analysis revealed that the 6.0-kb SI mRNA was expressed in the KAT line with intact sucrase-isomaltase activity. In contrast, 3.0-kb SI mRNA was expressed in suncus of the MI line with isolated sucrase deficiency. The 3.0-kb mRNA cosegregated with sucrase deficiency phenotype as an autosomal recessive trait. Sequence analysis revealed a 2-nucleotide deletion at position 2767-2768, which results in a frameshift and an immature termination codon. The cDNA of the MI line diverged from that of the KAT line at position 2865, having an 18-bp unique sequence followed by a poly(A) tail. The mutant cDNA encodes 922 amino acid residues which preserves the region for isomaltase but lacks that for whole sucrase. While the cells transfected with the plasmids expressing SI in the KAT line showed both sucrase and isomaltase activity, the plasmids expressing MI line cDNA showed only isomaltase activity. Thus it was concluded that the mutation in the SI gene was responsible for isolated sucrase deficiency in the MI line.

Amino Acid Sequence↗
PubMed1998

A novel approach to identify proteins associated with the inhibition of neurite growth.

In the present study, a novel combination of techniques was used to identify the genes that may be involved in the lack of axonal regeneration in the mammalian adult central nervous system (CNS). The key features of this approach are: (1) a functional assay that can be affected by antibody perturbation; (2) increased specificity of the polyclonal antiserum by adsorption; (3) the expression cloning of the genes from a lambdagt11 library; (4) amplification of the insert cDNA by PCR; and (5) the direct cycle sequencing of PCR products. In this culture assay system, neurons were plated directly on sections of the rat CNS. This assay system could be used to demonstrate the lack of neuronal attachment to or neurite extension over myelinated regions of the CNS (white matter). This prohibitive nature of the CNS sections could be masked by a rabbit polyclonal antiserum directed against rat CNS white matter. This data indicates that the anti-white matter antiserum recognizes and neutralizes inhibitory molecules on the surface of the sections. Making the assumption that the prohibitive antigen is associated with the cell membrane, the antiserum was adsorbed against a soluble protein fraction of the adult rat brain. This adsorption significantly increased the specificity of the antiserum as demonstrated by immunoblot methods. The adsorbed antiserum was then used to screen the cDNA library of the adult rat brain. The present report describes this novel combination of techniques allowing one to go from a functional tissue culture assay system to defining the molecular basis for the cellular interactions.

Adsorption↗
PubMed1998

Effects of thyroid status on expression of voltage-gated potassium channels in rat left ventricle.

OBJECTIVE: Thyroid hormone modifies cardiac action potentials and outward potassium currents directly and indirectly e.g. through beta-adrenergic signaling pathway. We thus examined the expression of six voltage-gated potassium channel alpha-subunits in the rat left ventricle under hypo- and hyperthyroid status, and tested roles of beta-adrenergic signaling pathway in their expressions under both status. METHODS: Hypothyroidism and hyperthyroidism were induced by administration of methimazole (MMI) for 4 weeks and by injection of L-thyroxine (T4) to the MMI-treated rats for the last 7 days, respectively. To distinguish the effects of T4 and the beta-adrenergic system, propranolol (Pro) was administered to the MMI-treated rats together with T4, and isoproterenol (Iso) was injected to MMI-treated rats for the last 7 days. The mRNA levels of Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3 in the left ventricles were determined by ribonuclease protection assay. RESULTS: MMI treatment induced hypothyroidism and resulted in a significant decrease in the mRNA levels of Kv1.5, Kv2.1 and Kv4.2 (19%, 77% and 61% of control value, respectively; n = 6, p < 0.05). T4 administration induced hyperthyroidism and cardiac hypertrophy, and it increased the Kv1.5 and Kv2.1 mRNA levels over the control value (212% and 140%, respectively; n = 6, p < 0.05). Kv4.2 mRNA level was restored to the control level by T4. In contrast, the Kv1.2 and Kv1.4 mRNA levels increased in hypothyroid rats (161% and 186% of control value, respectively; n = 6, p < 0.01) and decreased in hyperthyroid rats (14% and 33% of control value, respectively; n = 6, p < 0.01). The Kv4.3 mRNA level was not altered by thyroid status. Pro did not inhibit the T4-induced hypertrophy. Iso induced cardiac hypertrophy. Pro or Iso by itself did not alter Kv mRNA levels except for Kv1.2, the message of which was decreased by Iso. CONCLUSION: Thyroid hormone differentially regulates the expression of Kv1.4, Kv1.5, Kv2.1 and Kv4.2 mRNA levels in the rat left ventricle. This effect is not mediated through beta-adrenergic signaling pathway. On the other hand, the reduction in Kv1.2 mRNA level was associated with cardiac hypertrophy induced by T4 or Iso.

Adrenergic beta-Agonists↗
PubMed1998

Identification and characterization of potential cis-regulatory elements governing transcriptional activation of the rat tyrosine hydroxylase gene.

Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to 3,4-dihydroxy-L-phenylalanine, which is the first and rate-limiting step in catecholamine biosynthesis. We have previously shown that the cyclic AMP response element (CRE), an essential promoter element for both basal and cyclic AMP-inducible TH transcription, activates the promoter activity in a distance-dependent manner. To identify further cis-regulatory elements controlling TH gene expression, we analyzed the potential regulatory sequences by several approaches. First, using transient transfection assays, we examined the cell-specific promoter activities of TH-reporter gene constructs and a dopamine beta-hydroxylase (DBH)-reporter construct containing the 5' upstream sequences of the rat TH and human DBH genes, respectively, that had been shown to direct tissue-specific reporter expression in transgenic mice experiments. Second, DNase I footprinting analysis of the 503-bp proximal area of the rat TH gene identified seven footprinted regions that encompass the putative cis-regulatory motifs, including the CRE (domain 1), Sp1 (domain III), Octamer (domain IV), AP1 (domain V), AP2 (domain VI), and two potentially novel sequence motifs (domains II and VII). Footprinting patterns at these sites by nuclear proteins from TH-positive and -negative cell lines appeared to be similar. Third, site-directed mutagenesis demonstrates that domain III, but not domain II, critically contributes to the TH promoter activity. Furthermore, electrophoretic mobility shift, competition, and supershift assays demonstrate that domain III is an authentic Sp1 site and that the transcription factor Sp1 interacts with it. This and previous results suggest that the CRE and Sp1 site may synergistically activate TH transcription in a promoter context-dependent manner.

3T3 Cells↗
PubMed1998

Paired-like homeodomain proteins, Phox2a and Phox2b, are responsible for noradrenergic cell-specific transcription of the dopamine beta-hydroxylase gene.

Recently, a murine paired-like homeobox gene, Phox2a, has been identified whose product is critical for the development of several major noradrenergic neuron populations, including the locus coeruleus. In noradrenergic neurons, dopamine beta-hydroxylase (DBH) is a hallmark protein and catalyzes the conversion of dopamine to noradrenaline. Our previous studies have shown that a composite promoter (domain IV), residing at -185 to -150 bp upstream of the transcription start site, is critical for DBH transcription and is comprised of multiple cis-acting elements, including a cyclic AMP response element, a YY1 binding site, and two core motifs of the homeodomain (HD)-binding site. Here, we show that the HD-binding site residing within domain IV is a noradrenergic-specific cis-acting element. In contrast, the cyclic AMP response element is active in all cell lines tested. We provide evidence that Phox2a is expressed only in DBH-positive cell lines and interacts with the HD-binding site. Forced expression of Phox2a robustly activates DBH promoter activity in DBH-negative cell lines (>10-fold), but increased it only marginally (<50%) in DBH-positive cell lines. Furthermore, another protein factor with an identical HD, Phox2b, also activates DBH transcription with an efficiency comparable to that of Phox2a. In contrast, neither Phox2a nor Phox2b was able to transactivate tyrosine hydroxylase transcription, indicating that these transcription factors differentially activate catecholamine-synthesizing gene transcription. Together with the Phox2a knockout experiment, the studies described here make Phox2a and Phox2b the first strong candidate transcription factors for determining a neurotransmitter phenotype in vertebrates.

Animals↗
PubMed1998

Inductions of immediate early genes (IEGS) and ref-1 by human chorionic gonadotropin in murine Leydig cell line (MA-10).

The effect of human chorionic gonadotropin (hCG) on the expression of immediate early genes (IEGs) including all members of fos and jun family, and c-myc was studied using mouse Leydig cell line (MA-10 cells) by Northern blot analyses. In addition, the induction of ref-1 which enhances DNA binding of fos/jun proteins was also analyzed. HCG induced a rapid and transient expression of c-fos, fosB, c-jun, junB, junD and c-myc with a peak at 30 min to 1 h. In contrast, induction of fra-1 mRNA was delayed with a peak at 3 hr. However, fra-2 mRNA was immediately increased by hCG with a peak at 1 h. The ref-1 mRNA was expressed before the stimulation and its level was not altered by hCG at least for 8 hr. The differential induction of IEGs and continuous expression of ref-1 mRNA suggest an important role of their gene products on the regulation of Leydig cell function by hCG.

Animals↗