Biomedical subjects

H Tojo

Publications and source records attributed to H Tojo.

At least 37 records · Page 2Linked to original sources

PubMed2000

Co-injection of restriction enzyme with foreign DNA into the pronucleus for elevating production efficiencies of transgenic animals.

The microinjection method for production of transgenic farm animals requires specialized techniques and results in intolerably low production efficiencies. We investigated whether or not co-injection of foreign DNA constructs with restriction endonuclease into the pronucleus of mouse zygotes would improve the integration frequencies of foreign DNA into the host genome. Two kinds of DNA constructs that have no EcoRI site in their sequences were used for co-microinjection. With reference to the results of experiments in which EcoRI alone was injected at various amounts varying from 10(-9) to 10(-5) U/nucleus, the amount of 5x10(-8) U/nucleus that showed survival rate of 60.6% was used for the co-injection with DNA. Successful transgenesis of co-injected embryos was identified by DpnI-Bal31 digestion method for single embryos and by PCR method for pups born, respectively. The overall efficiency for the integration of foreign DNA in single embryos and live-born pups obtained by the co-injection procedures were 17.9% compared with 9.1% obtained by the injection of DNA alone. The results suggest that co-injection of foreign genes with restriction enzyme may elevate the integration rate of foreign genes into host genomes.

Animals↗

PubMed2000

Increased intestinal phospholipase A(2) activity catalyzed by phospholipase B/lipase in WBN/Kob rats with pancreatic insufficiency.

Male WBN/Kob rats derived from the Wistar strain spontaneously develop chronic pancreatitis as late as 3 months old. To assess the degree of disease severity, we compared the lipolytic enzyme levels in pancreas of 2-, 4-, and 6-month-old WBN/Kob rats fed isocaloric no fat (NF) and high fat (HF, 57% of total calories) diets and its pathology. Diet treatment did not significantly affect lipase and group Ib phospholipase A(2) (PLA(2)) levels in the pancreas at all ages. Development of chronic pancreatitis at the age of 4 and 6 months was consistent with the tendency of decreasing group Ib PLA(2) specific content determined by enzyme immunoassay and lipase activity, and the decreased number of group Ib PLA(2)-positive acinar cells. Pancreatic lipase and group Ib PLA(2) levels of 4-month-old WBN/Kob rats were significantly lower than those of control Wistar rats at age 4 months irrespective of diet. This allowed us to adopt 4-month-old WBN/Kob rats as a model of pancreatic insufficiency, which could be a useful tool to examine the role of gastrointestinal enzymes in lipid digestion. Ca(2+)-independent PLA(2) activity of brush border membrane-associated phospholipase B/lipase (PLB/LIP) in ileal mucosa increased significantly in 4-month-old WBN/Kob rats while its content and transcript levels remained constant, suggesting its activation at the enzyme level. In WBN/Kob rats fed the HF diet at age 4 months, PLA(2) activity catalyzed by PLB/LIP in the proximal ileal mucosa was four times the total PLA(2) activity in the intestinal lumen. These results indicate that PLB/LIP compensates for the depletion of pancreatic lipolytic enzymes in WBN/Kob rats with pancreas insufficiency.

Age Factors↗

PubMed2000

Comparative analysis of HOXC-9 gene expression in murine hemochorial and caprine synepitheliochorial placentae by in situ hybridization.

Mammalian placentae exhibit wide structural diversity among different species and are formed under intricate interplay between the embryonic trophoblast and the maternal endometrial cells. Increasing evidence in the literature indicates a possible role played by homeobox genes in the complex placental organogenesis. Although the expression of all HOX 9 paralogs has been demonstrated both in highly invasive murine hemochorial placentae and in non-invasive caprine synepitheliochorial placentae, no reports so far published in the literature described the patterns of gene expression of Hoxc-9 in the murine nor those of HOXC-9 in the caprine placenta at cellular levels. We carried out comparative analyses of the location and identity of the cells expressing Hoxc-9/HOXC-9 during various stages of placentation in the murine hemochorial and caprine synepitheliochorial placentae by means of in situ hybridization using murine Hoxc-9 or caprine HOXC-9 cRNA probe, respectively. The results demonstrated that Hoxc-9 mRNA was expressed at high levels in giant trophoblast cells of murine placentae on Days 12-19, but not on Day 8. Similar analysis of caprine Day 75 and Day 100 placentae revealed that the binucleate trophoblast cells that penetrate the uterine luminal epithelial cell layer, strongly expressed HOXC-9 mRNA. Although the functional significance of Hoxc-9/HOXC-9 gene expression in trophoblast cells remains to be elucidated, it was suggested that it might play a role in the regulation of invasiveness or endocrine activities in the murine giant trophoblast cells and/or the caprine binucleate trophoblast cells.

Age Factors↗

PubMed2000

Expression of myostatin gene in regenerating skeletal muscle of the rat and its localization.

The expression of myostatin mRNA was examined in regenerating skeletal muscle of the rat. Skeletal muscle regeneration was induced by injecting bupivacaine or hypertonic saline solution into the femoral muscle, and the tissues were collected 48 h after the treatment. In situ hybridization analysis revealed that the cells positive for myostatin message were localized in the regenerating area of the bupivacaine-treated tissues, where a numerous number of mononucleated cells were present. The myostatin-positive mononucleated cells contained both myogenic and nonmyogenic cells, as revealed by immunohistochemical staining for desmin and vimentin. Bupivacaine treatment to the testes resulted in no myostatin message expression in the testicular vimentin-positive cells, suggesting that the expression of myostatin message in vimentin-positive cells is a skeletal muscle-specific phenomenon. Furthermore, crushed muscle extract prepared from regenerating skeletal muscle had induced myostatin mRNA expression in skeletal muscle-derived fibroblasts in a dose-dependent manner. These results indicated that myostatin is expressed during skeletal muscle regeneration both in myogenic and nonmyogenic cells, and suggested that some factor(s) capable of inducing myostatin expression in fibroblasts are present in regenerating skeletal muscle.

Animals↗

PubMed2000

Establishment of fetal gonad/mesonephros coculture system using EGFP transgenic mice.

In developing mouse embryos, the Sertoli cells, Leydig cells, and seminiferous cords are differentiated in the XY gonads. The migration of mesonephric cells into the gonads is required during the developmental stage for seminiferous cord formation in the male gonads. In previous experiments, an organ coculture system has been used to examine morphologically developing gonads. However, by the process used in this system for fixing and staining the gonad/mesonephros complexes for examination, the kinetics of cell migration and the character of migrating cells cannot be observed. In the present study, we established an improved organ coculture system, using transgenic mice ubiquitously expressing Enhanced Green Fluorescent Protein (EGFP). In this system, time-dependent morphological changes in male-specific migration were observable in the gonad/mesonephros complex. The cell migration occurred at around 20 hr of coculture and began to spread at 25 hr with increases in the number of migrating cells occurring at 45 hr of coculture. No degenerative changes were detected at the end of coculture. Our results indicate that the present coculture system is very useful for investigating the mechanism of cell migration, as well as the characteristics of the migrating cells, in developing gonads. J. Exp. Zool. 286:320-327, 2000.

Animals↗

PubMed2000

Phospholipase A2-mediated superoxide production of murine peritoneal macrophages induced by chrysotile stimulation.

In the present study, we investigated how chrysotile-stimulated macrophages generate superoxide using murine peritoneal macrophages, with special attention to the modulatory role of phospholipase A(2) (PLA(2)). We examined the effects of the following inhibitors and antagonists for signaling molecules on the superoxide anion (O(2)(-)) production of chrysotile-stimulated macrophages: p-bromophenacyl bromide (pBPB) and mepacrine for PLA(2); islet-activating protein (IAP) for G-protein; H-7 for protein kinase C (PKC); AA861 for 5-lipoxygenase (5-LO); indomethacin for cyclo-oxygenase (COX); ETYA for both 5-LO and COX; hexanolamine PAF for platelet-activating factor (PAF). The PLA(2) and PKC inhibitors effectively inhibited the chrysotile-induced superoxide anion production of macrophages, but not the G-protein inhibitor, the 5-LO and COX inhibitors, and the PAF antagonist. We also examined the effects of the PLA(2) inhibitors on macrophages stimulated by phorbol 12-myristate 13-acetate (PMA) which directly activates PKC. The two structurally different PLA(2) inhibitors showed differential effects on the PMA-induced superoxide generation: pBPB inhibited it but mepacrine did not. These results suggested that (1) PLA(2) and PKC modulate the chrysotile-induced O(2) production, and (2) two different kinds of PLA(2) work upstream and downstream of PKC, but (3) G-protein, 5-LO and COX metabolites, and PAF have no modulatory role in the reaction.

Animals↗

PubMed2000

Elevations of group II phospholipase A2 concentrations in serum and amniotic fluid in association with preterm labor.

OBJECTIVE: The purpose of this study was to determine whether the elevation of secretory group II phospholipase A(2) concentration in the serum and amniotic fluid in preterm labor is associated with intrauterine inflammation. STUDY DESIGN: Serum and amniotic fluid were collected from women with preterm delivery (<37 weeks' gestation; n = 38) and term delivery (n = 20). Phospholipase activity was measured with a highly sensitive system that was based on reverse-phase high-performance liquid chromatographic separation of 9-anthracenylmethyl derivatives of fatty acids released by phospholipase A(2). The concentrations of immunoreactive isozymes (group I or II) of secretory phospholipase A(2) were assayed with a radioimmunoassay kit with a monoclonal antibody against human pancreatic phospholipase A(2) and splenic IIA phospholipase A(2). Localization of immunoreactive group II phospholipase A(2) in the amniotic membrane was determined by immunostaining visualized with the Vectastain ABC (Vector Laboratories, Inc, Burlingame, Calif) method. RESULTS: Enzymatic activities of phospholipase A(2) in the serum and amniotic fluid specimens obtained from patients in preterm labor with chorioamnionitis were significantly higher than those in specimens from patients in term labor. Significant elevations of phospholipase A(2) activities were observed in patients with preterm labor without histologically evident chorioamnionitis. The activity of phospholipase A(2) was clearly correlated with the concentration of the immunoreactive group II phospholipase A(2). Group II phospholipase A(2) was localized in amniotic cells obtained from patients with a pathologically determined diagnosis of chorioamnionitis. The predictive value for chorioamnionitis of the group II phospholipase A(2) concentration was relatively higher than the predictive values of the concentrations of C-reactive protein and interleukins 6 and 8. CONCLUSION: Significant elevations of group II phospholipase A(2) concentrations were detected in the serum and amniotic fluid of women with preterm labor. Group II phospholipase A(2) concentration may be a useful indicator for preterm labor, and phospholipid metabolism is certainly activated both in preterm labor and in apparent inflammatory diseases.

Amniotic Fluid↗

PubMed2000

Phosphorylation of mitogen-activated protein kinase cascade during early embryo development in the mouse.

The mitogen-activated protein kinase (MAPK) cascade is one of the most important signal transduction pathways that regulate the cell cycle in somatic cells. The present study examined the phosphorylation states of components in the MAPK cascade, Raf-1, MEK-1, and extracellular signal regulated kinases (ERKs), which are activated by mitogens, throughout early mouse embryo development and in cultured somatic cells generally. In somatic cells, Raf-1 and MEK-1 were phosphorylated at M-phase and dephosphorylated during interphase. ERKs were not phosphorylated at any stage during the cell cycle. These results were similar to previous findings for the first and second cell cycles of early mouse embryos. In contrast, after the four-cell stage, not only ERKs, but also Raf-1 and MEK-1, were not phosphorylated at any stage during the cell cycle in mouse early embryos. These results suggest that the MAPK cascade in mouse embryos is regulated by the same mechanism as in somatic cells before the two-cell stage, and that regulation is changed to an embryo-specific mechanism after the four-cell stage.

3T3 Cells↗

PubMed2000

Maturation/M-phase promoting factor: a regulator of aging in porcine oocytes.

Deterioration in the quality of mammalian oocytes during the metaphase-II arrest period is well known as "oocyte aging." Oocytes in which aging has occurred are called aged oocytes, and these oocytes show enhanced activation and higher fragmentation rates after parthenogenetic activation. Previously we showed that porcine aged oocytes had low maturation/M-phase promoting factor (MPF) activity, and we suggested that this low MPF activity contributed at least in part to the aging phenomena. In the present study, we examined the relationship between MPF activity and these aging phenomena by artificially regulating MPF activity in porcine metaphase-II-arrested oocytes. Since we have shown recently that aged porcine oocytes contain abundant phosphorylated inactive MPF, so-called pre-MPF, we used vanadate and caffeine, which affect the phosphorylation status of MPF, to regulate MPF activity. Incubation of 48-h-matured oocytes with vanadate for 1 h increased the phosphorylation of MPF and decreased MPF activity. The parthenogenetic activation and fragmentation rates were significantly increased compared with those of control oocytes. Conversely, treatment of 72-h-cultured aged oocytes with caffeine (last 10 h of culture) decreased the level of pre-MPF and elevated MPF activity. These oocytes revealed significantly lower parthenogenetic activation rates and a lower percentage of fragmentation than did untreated aged oocytes. These results indicate that not only the increased ability for parthenogenetic activation but also the increased fragmentation rate observed in porcine aged oocytes may be attributable in part to the gradual decrease in MPF activity during prolonged culture. Control of MPF phosphorylation with these agents may allow for some degree of manipulation of oocyte aging.

Animals↗

PubMed2000

Role of rapid focal activation in the maintenance of atrial fibrillation originating from the pulmonary veins.

Most episodes of focal atrial fibrillation (AF) can be initiated by premature beats originating from the pulmonary veins (PV). However, the role of rapid focal activation in the maintenance of AF is unclear. Thirty-two patients with focal AF who underwent focal ablation of triggering ectopic beats were studied. Bipolar electrograms from all four PVs were recorded simultaneously. The cycle length (CL) of RFA at sites that triggered AF was measured at AF onset, after 5 minutes of sustained AF, and just before the spontaneous termination of 32 episodes of nonsustained AF. Fifteen episodes of sustained AF (> 10 minutes) and 17 episodes of nonsustained AF (5-120 seconds, mean 56 +/- 59 seconds) were analyzed. In sustained AF, the mean CL of RFA in the PV from which it originated was not significantly different than in the other PVs, and RFA was continuously observed. In nonsustained AF, the mean CL of RFA in a PV from which it originated was significantly shorter than in other PVs and, when RFA disappeared, AF terminated. RFA in 1 PV induced RFA in another PV. In conclusion, widespread conduction of RFA from a PV at its source to the other sites may be necessary for the sustenance of AF. A PV interaction, a RFA triggering another, may be involved in the maintenance of AF. RFA arising from PVs is important not only as a trigger of onset, but also in the maintenance of AF.

Atrial Fibrillation↗

PubMed2000

Treatment of mixed atrial fibrillation and typical atrial flutter by hybrid catheter ablation.

Successful isthmus ablation of typical atrial flutter mixed with atrial fibrillation (AF) may favorably modify the subsequent course of paroxysmal AF. However, the source of ectopic beats triggering AF may be located in the pulmonary veins (PV). This study compared the results of combined isthmus and focal ablation with ablation limited to the isthmus in patients with mixed AF and typical atrial flutter. Thirty patients with typical atrial flutter and AF were treated. Ablation limited to the isthmus was performed in 14 patients (group A), and 16 patients underwent focal ablation of triggering ectopic beats combined with isthmus ablation (group B). Successful linear ablation of the isthmus was accomplished in all patients. In group A, AF was eliminated in 4 patients (29%) after isthmus ablation. In group B, the origin of 26 foci triggering AF (1 focus in 38% of patients, 2 foci in 31%, 3-4 foci in 31%) was found in the PV in 93% (left superior: 46% left inferior: 21%, right superior: 25%) and the right atrium in 7% of instances. AF was eliminated in 11 patients (69%) after ablation of these foci. The success rate in group B was significantly higher than in group A (P < 0.05). In conclusion, in cases of mixed AF and typical atrial flutter, episodes of AF originated from PV foci in > 90% of instances. These findings suggest that isthmus ablation combined with PV focal ablation may be effective in mixed AF and typical atrial flutter.

Atrial Fibrillation↗

PubMed2000

New technique for simultaneous catheter mapping of pulmonary veins for catheter ablation in focal atrial fibrillation.

INTRODUCTION: Most focal atrial fibrillation (AF) can be triggered by premature beats from pulmonary veins (PVs), and ablation of these foci could cure AF. However, it is difficult to locate the trigger points of PVs using only one mapping catheter. The purpose of the present study was to investigate the efficacy of using four mapping catheters in four PVs simultaneously in the ablation of focal AF. METHODS AND RESULTS: Thirty-two patients with frequent attacks of paroxysmal AF triggered by PV foci were included. After a transseptal procedure, three 2-french microcatheters and one 7-french catheter for ablation were placed into each of the PVs, and mapping of the four PVs was performed simultaneously. Fifty-eight foci were identified; 51 triggers (88%) originated from the PV and 7 (12%) from atrial tissue. The trigger points of AF were found in a single focus in 14 patients, in 2 foci in 12 patients, and in 3-4 foci in 6 patients. During a mean follow-up period of 10 +/- 4 months, ablation eliminated AF without drugs in 86, 50 and 33% of the patients with 1, 2 and 3-4 targeted PVs, respectively; 20 patients (63%) were successfully ablated. Age, history of AF, the dimension of the left atrium and the number of focal origins were significant predictors of success. CONCLUSION: The technique of simultaneous mapping of PVs using quadruple catheters is a feasible and effective method for mapping the trigger points and ablation of focal AF originating from PVs.

Adult↗

PubMed2000

Identification of skeletal muscle satellite cells by transfecting EGFP driven by skeletal alpha-actin promoter.

In isolating skeletal muscle satellite cells, sometimes a problem is encountered in removing contaminating nonmyogenic cells. In the present study, we constructed a novel vector, pSKA-EGFP, which achieves the expression of enhanced green fluorescent protein (EGFP) exclusively in myogenic cells under the control of skeletal alpha-actin promoter when transfected to primary cultured cells from skeletal muscle. Cells from rat skeletal muscle positive for EGFP after transfecting with pSKA-EGFP were all positive for desmin and none of the nonmyogenic cells expressed EGFP, indicating that the expression of EGFP is specific to myogenic cells. Among the cells positive for EGFP were proliferating cells, presumably satellite cells. In addition, EGFP positive cells derived from horse skeletal muscle after transfecting pSKA-EGFP in vitro formed multinuclear myotubes, indicating that myogenic expression of EGFP driven by skeletal alpha-actin was achieved also in the equine cells. These results indicated that pSKA-EGFP vector will be useful in identifying and following up the satellite cells in real time, and also permit us to isolate satellite cells in combination with fluorescence-activated cell sorting (FACS).

Actins↗

PubMed2000

In vitro studies on PGC or PGC-like cells in cultured yolk sac cells and embryonic stem cells of the mouse.

The present study aims: 1) to determine those conditions which promote the proliferation of primordial germ cells (PGCs) of the migratory phase in the yolk sac; and 2) to examine the effects of yolk sac cells as a feeder layer under the conditions mentioned above upon the embryonic stem (ES) cells (R1) with high potential for entering the germ line in vivo in chimeras. In murine yolk sac cells obtained on Day 10.5-11.5 of pregnancy and cultured in a modified Dulbecco's modified Eagle's medium (DMEM-plus/20: the postfix represents the concentration of FBS added in percentage), many cells exhibited strong immunoreactivities to the monoclonal antibodies 4C9 and 2C9 which are known to react with PGC specifically. Both the 4C9- and the 2C9-positive cells were sensitive to the treatment with busulfan added in vitro, supporting the supposition that they were PGCs. The respective numbers of the 4C9- and the 2C9-positive cells increased approximately 4 and 12 times when they were cultured in DMEM-plus/20 fortified with SCF, LIF, bFGF and TNF-alpha (DMEM-NT/20). When the R1 cells were cultured in the yolk sac-conditioned DMEM-NT/20 medium on the laminin substratum, the entire colonies were faintly stained with 4C9 but not with 2C9. At times solitary ES cells migrated out from the colonies, and reacted strongly with 4C9. When yolk sac cells and R1 cells were cultured on the two sides of a collagen-coated membrane, the yolk sac cells being feeder cells, some R1 cell colonies were intensely stained as a whole with either the 4C9 or the 2C9 antibody, suggesting that these colonies might be composed of cells clonally derived from stem cells which either had been destined to become the germ line cells or had already acquired cellular characteristics close to PGCs. It was tentatively concluded that the R1 cell population contained, as judged from the immunoreactivities, germ-cell-like cells, and that the yolk sac cells and/or their secretory products might facilitate the proliferation of, or the conversion of R1 cells to, the germ-cell-like cells.

Alkylating Agents↗

PubMed1999

Differential regulation of immediate early gene expression in preadipocyte cells through multiple signaling pathways.

Using digoxigenin (DIG)-based differential hybridization, a series of immediate early genes (IEG) was identified following the adipogenic stimulation in 3T3-L1 preadipocyte cells. Most of the known IEGs were identified as well as new members such as zf9 and Stra13. To delineate possible signaling pathways accounting for these gene expression, a subset of specific kinase inhibitors, SB203580, PD98059, rapamycin, LY294002, and Ro-32-0432, which inhibit p38 (HOG), MEK (MAPKK), S6 kinase, PI3 kinase, and protein kinase C (PKC), respectively, were employed. The IEGs were classified into three categories according to their susceptibility to the inhibitors. Expression of the first group (c-fos, jun-B, egr-1, tis11, tis21, thrombospondin-1, erp, thyroid hormone receptor [N-10], cyr61, and zf9) was mainly dependent on PKC and MEK pathways, while that of the second class (gene33 and tis10) exhibited an additional dependence on PI3 kinase pathways. The third one (Id-3, gly96, and Stra13) was characterized in that none of these inhibitors interfered with gene expression. Our results suggest that the induction of IEGs by the adipogenic stimuli is mediated by common as well as distinct signaling pathways.

3T3 Cells↗

PubMed1999

cDNA cloning and expression analysis of mouse zf9, a Krüppel-like transcription factor gene that is induced by adipogenic hormonal stimulation in 3T3-L1 cells.

Using a differential hybridization method, we have cloned a zinc finger transcription factor gene whose expression was enhanced by adipogenic hormones in preadipocyte 3T3-L1 cells. Cloning of this gene revealed that it encodes a mouse homologue of rat Zf9 and human CPBP/GBF, previously identified as a wound-induced transcription factor and GC-rich binding protein, respectively. The mRNA for this clone consisted of 0.9 kb coding region and 3.2 kb long 3' untranslated region. Northern blot analysis revealed that it was ubiquitously expressed, among adult tissues, in which abundant expression was observed in lung, ovary and thymus. The transcript was transiently induced by different stimuli such as serum, cAMP and 12-O-tetradecanoylphorbol 13-acetate. Nuclear run-on and RNA synthesis inhibitor chase experiments indicated that the transient induction of the mRNA was regulated both at transcriptional and post-transcriptional levels.

3T3 Cells↗

PubMed1999

A prespore-cell-inducing factor in Dictyostelium discoideum: its purification and characterization.

Under starvation conditions, amoebae of Dictyostelium discoideum aggregate to form multicellular masses; the aggregates are then initiated to differentiate. We have reported previously that a signal substance exists in conditioned medium of D. discoideum, and we named it prespore-cell-inducing factor (psi, Psi factor) [Oohata, Nakagawa, Tasaka, and Fujii (1997) Development 124, 2781-2787]. The factor can induce isolated amoebae to differentiate into prespore cells. Moreover, we suggested that it caused not only cell differentiation but also cell division. In the present study, we have purified Psi factor from the conditioned medium and characterized it. The purified Psi factor induced both prespore cell differentiation and cell division of prespore cells. Its apparent molecular mass was 180 kDa by gel filtration and 106 kDa by SDS/PAGE. Based on these results, Psi factor exists as a dimer in normal conditions. Periodic acid/Schiff staining showed that Psi factor was a glycoprotein. It was ascertained by Edman degradation that Psi factor is blocked at the N-terminal. Treatment with pyroglutamate aminopeptidase removed the N-terminal block and allowed determination of the amino-acid sequence of Psi factor. Moreover, three internal amino-acid sequences were determined in limited proteolysis experiments using trypsin and endoproteinase Lys-C. The homology search for these sequences supports the fact that Psi factor is a novel differentiation factor.

Amino Acids↗

PubMed1999

Endometrial expression of cellular protooncogene c-ski and its regulation by estradiol-17beta.

The expression of the cellular protooncogene c-ski was examined in the rat uterus. In situ hybridization revealed that c-ski mRNA was expressed in the uterus of the adult rat on the day of estrous and localized mainly in the luminal and glandular epithelia. To test the possibility that the expression of c-ski mRNA is induced by estrogen, rats were ovariectomized and estradiol-17beta (E2) was injected. The expression of c-ski mRNA was upregulated 3 h after E2 treatment, reaching the highest level at 6 h and this persisted until 24 h; the E2-induced expression of c-ski mRNA was restricted to the luminal and glandular epithelia. These results suggest that the c-ski gene plays a role in uterine epithelial cell proliferation and mediates the proliferative action of E2.

Animals↗