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Biomedical subjects

H Matsuo

Publications and source records attributed to H Matsuo.

At least 235 records · Page 13Linked to original sources
PubMed1998

Increased plasma adrenomedullin concentrations during cardiac surgery.

1. Adrenomedullin (AM), a potent hypotensive peptide, was originally isolated from human phaeochromocytoma. Plasma AM concentrations are elevated in hypertension, heart failure and renal failure in proportion to the severity of the disease. This study was performed to investigate the pathophysiological significance of AM during cardiac surgery. 2. Serial blood samples were obtained from patients undergoing cardiac surgery and plasma AM concentrations were determined by specific radioimmunoassay. 3. Plasma AM concentrations did not increase with anaesthesia or surgery (n = 9). Plasma AM concentrations gradually increased during cardiopulmonary bypass and after pulmonary reperfusion. After pulmonary reperfusion, plasma AM concentrations increased further. In addition, we measured plasma AM concentrations in the pulmonary vein (n = 8) and coronary sinus (n = 8) to examine the contribution of the lungs and heart to the increase in circulating AM concentrations after cardiopulmonary bypass. However, no significant differences were seen in plasma AM concentrations of the pulmonary vein or the coronary sinus and the aorta. Peak AM concentrations during cardiac surgery correlated with duration of surgery. Elevated plasma AM levels during and after surgery began to decline next day after surgery and returned to normal levels 7 days after surgery. 4. These results demonstrate that plasma AM concentrations increase during cardiac surgery and that the duration of surgery may be related to the changes in AM concentrations. Taken together with recent findings that vascular endothelial cells and vascular smooth muscle cells actively produce AM, these results suggest that plasma AM during cardiac surgery may act as a vasodilatory hormone.

Adrenomedullin↗
PubMed1998

A simple and early prognostic index for acute renal failure patients requiring renal replacement therapy.

Recent advances in technology have not substantially changed the high mortality rate associated with acute renal failure (ARF). To obtain a simple, valid prognostic index, we retrospectively evaluated the relative importance of demographic data, causes (acute insults) of renal failure, and comorbid clinical conditions for the outcome in 102 ARF patients who received renal replacement therapy with an overall mortality rate of 65% (66 of 102). There were no significant differences between survivors and nonsurvivors in age and gender. Mortality according to acute insults was similar to that of the whole population studied. Of the 10 clinical conditions at the time of the first renal replacement therapy, mechanical ventilation (p = 0.0002), cardiac failure (p = 0.0006), hepatic failure (p = 0.003), central nervous system dysfunction (p = 0.005), and oliguria (p = 0.04) were found to be significantly related to mortality by univariate analysis. Furthermore, multivariate analysis demonstrated that only mechanical ventilation, cardiac failure, and hepatic failure were significant risk factors. Survival was directly related to the number of significant variables in univariate analysis: zero, 89% (8 of 9); one, 62% (21 of 34); two, 19% (5 of 27); three, 10% (2 of 20); four, 0% (0 of 8); five, 0% (0 of 4). This simple and early prognostic index, derived from the assessment of clinical conditions which were easily determined at the patient's bedside, could be useful for outcome prediction in ARF patients requiring renal replacement therapy.

Acute Kidney Injury↗
PubMed1998

Secretion patterns of brain natriuretic peptide and atrial natriuretic peptide in patients with or without pulmonary hypertension complicating atrial septal defect.

UNLABELLED: BACKGROUND This study was designed to investigate plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with atrial septal defect (ASD), whose right ventricular loading patterns vary from simple volume overloading to both volume and pressure overloading. METHODS AND RESULTS: Plasma ANP and BNP in the pulmonary artery were measured in 31 adult patients with ASD and 11 control subjects. On the basis of the presence of pulmonary hypertension (PH, mean pulmonary arterial pressure >20 mm Hg), patients with ASD were divided into two groups, patients without PH (group 1, n = 21) and those with PH (group 2, n = 10). Cardiac catheterization was performed to measure mean pulmonary arterial pressure and pulmonary blood flow. Plasma ANP was significantly higher in both group 1 and group 2 than in the control group. Plasma BNP and BNP to ANP (BNP/ANP) ratio were significantly higher in group 2 than in the control group, although they were not significantly elevated in group 1. Plasma ANP positively correlated with the degree of pulmonary blood flow (r = 0.54, p < 0.01), whereas plasma BNP positively correlated with the magnitude of mean pulmonary arterial pressure (r= 0.73, p < 0.001). BNP/ANP >1 was a powerful marker for the presence of PH (sensitivity 90%, specificity 90%). CONCLUSIONS: Plasma ANP levels were elevated in adult patients with ASD regardless of PH. In contrast, plasma BNP levels were elevated in proportion to the severity of PH complicating ASD. Thus BNP and ANP may represent differing aspects of cardiac response to right ventricular overload in patients with ASD.

Adult↗
PubMed1998

Purification and characterization of a puromycin-hydrolyzing enzyme from blasticidin S-producing Streptomyces morookaensis.

Blasticidin S-producing Streptomyces morookaensis JCM4673 produces an enzyme which inactivates puromycin (PM) by hydrolyzing an amide linkage between its aminonucleoside and O-methyl-L-tyrosine moieties [Nishimura et al. (1995) FEMS Microbiol. Lett. 132, 95-100]. In this study, we purified to homogeneity the enzyme from the cell-free extracts of S. morookaensis. The molecular weight of PM-hydrolyzing enzyme, estimated by SDS-PAGE and gel filtration, was 68 and 66 kDa, respectively, suggesting that this protein is monomeric. The PM-hydrolyzing activity was strongly inhibited by Zn2+, Fe2+, Cu2+, Hg2+, and N-bromosuccinimide, but was stimulated by DTT. The optimum pH and temperature for PM-hydrolyzing activity were 8.0 and 45 degrees C, respectively. Several L-aminoacyl-beta-naphthylamides were good substrates for the enzyme, suggesting that the PM-inactivating enzyme has an aminopeptidase activity. The N-terminal sequence of the first 14 amino acids (Val-Ser-Thr-Ala-Pro-Tyr-Gly-Ala-Trp-Gln-Ser-Pro-Ile-Asp) of the enzyme showed no significant homology with any published hydrolase sequences.

Aminopeptidases↗
PubMed1998

Increased plasma concentration of adrenomedullin in patients with subarachnoid hemorrhage.

UNLABELLED: Adrenomedullin (AM) is a potent hypotensive peptide originally identified in pheochromocytoma tissues. Impaired cardiovascular conditions, such as hypertension, myocardial infarction, and septic shock, stimulate production of AM. This study was performed to determine whether subarachnoid hemorrhage (SAH) altered plasma AM concentration. Plasma concentrations of AM in 17 patients with SAH were measured for 2 wk after the onset of SAH by AM-specific radioimmunoassay. Plasma concentrations of AM were increased in patients with SAH throughout the study period, compared with those in control subjects. Plasma concentrations of AM in patients classified as Hunt and Kosnik grade III or IV were significantly higher than those classified as Hunt and Kosnik grade I or II on the day of and the day after the onset of SAH. However, plasma concentrations of AM were unaffected by angiographic vasospasm. These findings suggest that plasma concentrations of AM are increased in patients with SAH and may reflect the severity of SAH. IMPLICATIONS: Adrenomedullin has been reported to affect the cerebral circulation. This study was performed to determine whether subarachnoid hemorrhage, a typical cerebrovascular disorder, altered plasma adrenomedullin concentrations. We found that plasma adrenomedullin concentrations increased in patients with subarachnoid hemorrhage, although no relationship was found between plasma adrenomedullin concentration and angiographic vasospasm. Plasma adrenomedullin concentration may reflect the severity of hemorrhage.

Adrenomedullin↗
PubMed1998

A new device for selective removal of CD4+ T cells.

To control antigen (Ag)-specific immune cells is important in the treatment of autoimmune diseases. In particular, a direct solution may be obtained by controlling the CD4+ cell function that controls the immune response of autoimmune T cells. Thus, a technique to selectively remove CD4+ cells has been developed, based on the consideration that the immune system may possibly be modified by selectively removing the CD4+ cells by means of extracorporeal circulation. The currently developed device to selectively remove CD4+ cells uses a material made of nonwoven fabric with monoclonal antibodies immobilized on the surface. With this device, removal of only CD4+ cells from human mononuclear cells suspension can be accomplished. Moreover, CD4+ cells can be specifically removed from peripheral whole blood by direct perfusion. This review outlines a series of procedures for selective cell removal and the results of our research.

Animals↗
PubMed1998

Efflux transport of tolbutamide across the blood-brain barrier.

In an attempt to determine the reason for the low brain distribution of tolbutamide, we have demonstrated the transport of tolbutamide from the brain to the blood via a non-P-glycoprotein efflux transport system which is inhibited by sulphonamides. We evaluated the directional transport of tolbutamide across the blood-brain barrier by means of an in-vivo brain-tissue distribution study and experiments on in-vitro transcellular transport and uptake in cultured mouse-brain capillary endothelial cells (MBEC4). The brain-to-unbound-plasma concentration ratio of [14C]tolbutamide increased in the presence of high concentrations of unlabelled tolbutamide or sulphonamide at steady-state in-vivo. The brain-to-blood concentration ratios of [14C]tolbutamide were very low compared with that of [3H]propranolol obtained by in-vivo integration plot analysis. From the in-vitro transcellular transport study using a monolayer of MBEC4 cells, we found that the abluminal-to-luminal flux of [14C]tolbutamide was higher than the reverse flux. Both luminal-to-abluminal and abluminal-to-luminal transport of tolbutamide were saturable. The maximum transport rate (Jmax), the half-saturation concentration (Kt), and the first-order rate constant (kd) were 65.9 +/- 29 pmol min(-1) (mg protein)(-1), 7.54 +/- 4.4 microM, and 4.89 +/- 0.34 microL min(-1) (mg protein)(-1), respectively, for luminal-to-abluminal transport, and 128 +/- 66 pmol min(-1) (mg protein)(-1), 5.59 +/- 4.2 microM, and 4.43 +/- 0.86 microL min(-1) (mg protein)(-1) , respectively, for abluminal-to-luminal transport. At therapeutic plasma concentrations of tolbutamide (1-16.9 microM), the efflux rate would be faster than the influx rate. The estimated net efflux was consistent with the very low in-vivo brain distribution of tolbutamide. The efflux process observed in MBEC4 cells was inhibited by sulphonamides such as sulphaphenazole, sulphamethoxazole and sulpha-dimethoxine whereas the steady-state uptake of [14C]tolbutamide was not affected by either cyclosporin or verapamil, specific inhibitors of P-glycoprotein. These findings suggest that tolbutamide is partly transported from the brain via the non-P-glycoprotein-efflux transport system, which is inhibited by sulphonamides.

Animals↗
PubMed1998

P-glycoprotein-mediated transport of itraconazole across the blood-brain barrier.

The mechanism for the accumulation of itraconazole (ITZ) in its elimination from the brain was studied in rats and mice. The concentration of ITZ in liver tissue declined in parallel with the plasma ITZ concentration until 24 h after intravenous injection of the drug (half-life, 5 h); however, the ITZ in brain tissue rapidly disappeared (half-life, 0.4 h). The time profiles of the brain/plasma ITZ concentration ratio (Kp value) showed a marked overshooting, and the Kp value increased with increasing dose; these phenomena were not observed in the liver tissue. This finding indicates the occurrence of a nonlinear efflux of ITZ from the brain to the blood. Moreover, based on a pharmacokinetic model which hypothesized processes for both nonlinear and linear effluxes of ITZ from the brain to the blood, we found that the efflux rate constant in the saturable process was approximately sevenfold larger than that in the nonsaturable process. The Kp value for the brain tissue was significantly increased in the presence of ketoconazole or verapamil. The brain Kp value for mdr1a knockout mice was also significantly increased compared with that of control mice. Moreover, the uptake of vincristine or vinblastine, both of which are substrates of the P glycoprotein (P-gp), into mouse brain capillary endothelial cells was also significantly increased by ITZ or verapamil. In conclusion, P-gp in the brain capillary endothelial cells participates in a process of active efflux of ITZ from the brain to the blood at the blood-brain barrier, and ITZ can be an inhibitor of various substrates of P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Increased plasma adrenomedullin levels in patients with acute myocardial infarction in proportion to the clinical severity.

OBJECTIVES: To investigate the pathophysiological role of adrenomedullin in myocardial infarction. PATIENTS AND DESIGN: Plasma concentrations of adrenomedullin, atrial natriuretic factor, and brain natriuretic peptide were measured by radioimmunoassay in 31 patients with acute myocardial infarction over four weeks, and in 44 normal subjects. RESULTS: In patients with acute myocardial infarction, plasma adrenomedullin reached a peak of (mean (SD) 14.0 (9.0) pmol/l at 24 hours after the onset of symptoms and remained increased at all sampling points except the four week point compared with the value in normal subjects (5.0 (2.0) pmol/l). Adrenomedullin concentrations on admission were higher in patients from Killip class II, III, and IV than class I, and correlated positively with peak plasma creatine kinase and left ventricular end diastolic volume index, and negatively with left ventricular ejection fraction. The values from 12 to 48 hours were negatively correlated with systemic vascular resistance index. During the time course studied, adrenomedullin concentrations were positively correlated with atrial natriuretic factor (r = 0.40, p < 0.001) and brain natriuretic peptide (r = 0.53, p < 0.001). CONCLUSIONS: Plasma adrenomedullin concentrations increased in the acute phase of myocardial infarction in proportion with clinical severity suggesting that adrenomedullin may play an important role in the pathophysiology of myocardial infarction.

Adrenomedullin↗
PubMed1998

Measurement of plasma and urinary adrenomedullin in patients with IgA nephropathy.

In this study, we measured plasma and urinary adrenomedullin (AM) concentrations in 47 patients with IgA nephropathy. Controls were 39 healthy volunteers. Plasma and urinary AM values were measured by specific radioimmunoassay. The plasma AM concentrations were higher, and the urinary AM levels were lower in patients with IgA nephropathy than in healthy volunteers. Plasma AM concentrations showed a positive correlation with serum creatinine and blood urea nitrogen, whereas urinary AM levels correlated negatively with serum creatinine and blood urea nitrogen. The plasma AM concentrations showed a positive correlation with fractional excretions of sodium and potassium. Renal biopsy specimens of patients without renal failure were scored for activity (percentage of glomeruli demonstrating cellular crescent formation, degree of mesangial proliferation and interstitial infiltration; total score = 9). Urinary AM levels were shown to be lower in the group with a high activity (score 3-9) as compared with the group with a low activity (score 0-2) based on renal biopsy. Thus, urinary levels of AM are affected by the degree of the activity in IgA nephropathy, and AM may participate in the pathophysiology of IgA nephropathy.

Adrenomedullin↗
PubMed1998

Plasma and urinary levels of adrenomedullin in chronic glomerulonephritis patients with proteinuria.

In this study, we measured levels of plasma and urinary adrenomedullin (AM) in 37 patients with chronic glomerulonephritis including minimal change nephrotic syndrome, focal segmental glomerulosclerosis or membranous nephropathy that can induce severe proteinuria. Thirty-nine healthy volunteers were enrolled as controls. Plasma and urinary AM levels were measured by an AM-specific radioimmunoassay. Plasma AM concentrations were higher and urinary AM levels were lower in patients with chronic glomerulonephritis than in healthy volunteers. Patients were divided into two groups according to urinary excretion of protein for 24 h (UPro, g/day) which reflects the disease activity or glomerular damage of the glomerulonephritis (group I: Upro < 1, group II: Upro >= 1). Plasma AM levels positively and urinary AM-levels negatively correlated with the degree of proteinuria. These results suggest that plasma and urinary AM levels in patients with chronic glomerulonephritis reflect the disease activity or glomerular damage represented by the degree of proteinuria.

Adrenomedullin↗
PubMed1998

Effect of immunotherapy on the production of eosinophil adhesion-inducing activity from mononuclear cells in house-dust-mite-sensitive bronchial asthma.

An initial step of eosinophil (EOS) accumulation in the sites of allergic inflammation is the adhesion to endothelial cells. There is increasing evidence that immunotherapy (IT) modulates the production of cytokines from mononuclear cells and hence attenuates allergic inflammation. To examine whether IT modifies the production of factor(s) which induce EOS adhesion, peripheral blood mononuclear cells (PBMC) from house-dust-mite-sensitive asthmatics treated with or without IT were cultured for 96 h in the presence or absence of 1/microg/ml Dermatophagoides farinae antigen. EOS were isolated from the peripheral blood of healthy subjects. EOS adhesion-inducing activity (EAIA) in the PBMC culture supernatants was examined by the ability to modify EOS adhesion to paraformaldehyde-fixed human umbilical vein endothelial cells (HUVEC) which were stimulated with IL-4 plus TNF-alpha. In asthmatics without IT, the addition of D. farinae antigen significantly promoted the production of EAIA from PBMC (EOS adhesion: 22.4+/-13.1% by medium control vs. 30.5+/-18.9% by D. farinae, n=10, p=0.023). This enhancing effect was blocked by an anti-beta2-integrin antibody. In contrast, the addition of D. farinae did not modulate EAIA production from PBMC in asthmatics treated with IT (23.1+/-10.3% vs. 21.5+/-12.3%, n=10, p=NS). These results suggest that IT induces the inhibition of antigen-dependent production of EAIA from PBMC. This may contribute to the inhibitory effect of IT on eosinophil recruitment in allergic inflammation.

Animals↗
PubMed1998

Hepatic infarction caused by an embolus from an atherosclerotic lesion--a case report.

Although it has been reported that emboli from atherosclerotic disease may be more frequent than commonly appreciated, hepatic infarction caused by an arterial embolus is an unusual but serious complication. The authors describe a patient who had a secondary liver infarct during anticoagulant treatment for cerebral infarction. The thrombus causing the liver infarction was detected as a low echoic mass by transesophageal echocardiography at the right coronary sinus.

Aged↗
PubMed1998

Production and secretion of adrenomedullin in cultured rat cardiac myocytes and nonmyocytes: stimulation by interleukin-1beta and tumor necrosis factor-alpha.

The present study investigated the secretion level and gene expression of adrenomedullin (AM), a novel vasorelaxant peptide, in cultured neonatal rat cardiac myocytes and nonmyocytes, and the effects of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF alpha) on its production and secretion in these cells. Under serum-free conditions, both myocytes and nonmyocytes secreted immunoreactive (ir-) AM into the culture medium in a time-dependent manner. The secretion rates of ir-AM from myocytes and nonmyocytes per 10(5) cells were almost equivalent. The expression of AM messenger RNA was also observed in cultured myocytes and nonmyocytes. The peptide secretion and messenger RNA level of AM in cardiac myocytes were increased after stimulation with IL-1beta. In nonmyocytes, IL-1beta and TNF alpha remarkably augmented both the release of ir-AM into the medium and AM gene expression after 24 and 48 h of incubation. These observations indicate that cardiac ventricular cells (i.e. myocytes and nonmyocytes) actively produce AM and also suggest that cytokines such as IL-1beta and TNF alpha regulate the gene expression and secretion of this peptide in the ventricles. On the basis of these results and the findings that IL-1beta and TNF alpha are involved in heart failure and cardiac hypertrophy, AM may play a role as an autocrine/paracrine modulator in some cardiac disorders.

Adrenomedullin↗
PubMed1998

Regulation of adrenomedullin production in rat endothelial cells.

Adrenomedullin (AM) is a potent vasorelaxant peptide recently identified in extracts of pheochromocytoma. We have found that AM is actively secreted from endothelial cell (EC) and vascular smooth muscle cell (VSMC). To elucidate the function of AM secreted from EC, the effects of 43 substances on secretion of AM from cultured rat EC were examined in this study. We first confirmed that synthesized AM was not stored but constitutively secreted from EC, indicating that the amount secreted could be used as an index of AM synthesis in EC. EC secreted AM at a rate 5.8 times higher than VSMC, and AM gene transcription in EC significantly contributed to the total aortic AM messenger RNA. Tumor necrosis factor, interleukin-1, and lipopolysaccharide augmented AM secretion from EC, showing cooperative effects, which suggests that AM secreted from EC participates in the induction of hypotension in septic shock. Transforming growth factor beta1 and FCS suppressed AM secretion but stimulated endothelin-1 (ET-1) secretion. Thrombin potently stimulated AM secretion from EC but suppressed it from VSMC. Thyroid hormone and phorbol ester increased AM and ET-1 secretion but to a lesser extent. Interferon-gamma inhibited AM secretion from EC, whereas oxidized LDL stimulated it. Regulation of AM production in EC is found to be similar to that of VSMC with several exceptions, but AM and ET-1 production in EC are deduced to be controlled independently and by different mechanisms. AM stimulates cAMP production in EC, though receptors expressed on cultured rat EC are not specific to AM but to calcitonin gene-related peptide. Based on these findings, AM production in EC is thought to be regulated by a variety of substances coming from blood and neighboring cells, and the secreted AM is deduced to dilate blood vessels as an endothelium-derived relaxing factor competing with ET-1.

Adrenal Cortex Hormones↗
PubMed1998

Adrenomedullin production in fibroblasts: its possible function as a growth regulator of Swiss 3T3 cells.

In addition to endothelial cells and vascular smooth muscle cells, we demonstrated that adrenomedullin (AM) is synthesized and secreted from fibroblasts, Swiss 3T3, Hs68, and NHLF cells, in a native and biologically active form. Synthesis and secretion of AM from these fibroblasts was regulated by inflammatory cytokines, such as tumor necrosis factor and interleukin-1, lipopolysaccharide, growth and differentiation factors, and hormones in a manner similar to that of vascular smooth muscle cells and endothelial cells. Tumor necrosis factor-alpha, interleukin-1beta, and dexamethasone elevated AM secretion, whereas transforming growth factor-beta1 and interferon-gamma suppressed it in these three fibroblasts. Swiss 3T3 cells were shown to express receptors specific for AM by both cAMP production and receptor binding assay, and AM was found to stimulate DNA synthesis of quiescent cells through the cAMP-mediated pathway. AM secreted from Swiss 3T3 cells was also confirmed to augment cAMP production and DNA synthesis in the cells themselves. These effects were inhibited by a neutralizing monoclonal antibody against AM. These findings raise the possibility that AM functions as a growth regulator in the case of Swiss 3T3 cells. As AM receptors are widely distributed, AM secreted from fibroblast may play a role as a local regulator in mesenchymal cells of inflammatory or wounded regions.

3T3 Cells↗
PubMed1998

Up-regulation by progesterone of proliferating cell nuclear antigen and epidermal growth factor expression in human uterine leiomyoma.

Uterine leiomyoma is the most common smooth muscle cell tumor of the myometrium. Estrogen and progesterone (P4) are believed to be physiological regulators of leiomyoma growth. We recently showed that Bcl-2 protein, an apoptosis-inhibiting gene product, was abundantly expressed in leiomyoma relative to its expression in the normal myometrium and that Bcl-2 protein expression in cultured leiomyoma cells was up-regulated by P4, but down-regulated by 17 beta-estradiol (E2). To further characterize the molecular mechanism of sex steroidal regulation of leiomyoma growth, we examined the effect of menstrual phase on proliferating cell nuclear antigen (PCNA) expression in leiomyoma and investigated whether sex steroids could influence PCNA expression in leiomyoma cells cultured under serum-free conditions by immunoblot and immunohistochemical analyses. As epidermal growth factor (EGF) has been shown to mediate estrogen action and to play a crucial role in regulating leiomyoma growth, we also investigated the effects of sex steroids on the expression of EGF and EGF receptor (EGF-R) in cultured leiomyoma cells. The PCNA labeling index in leiomyomas was much greater in the secretory, P4-dominated, phase than in the proliferative phase of the menstrual cycle and was significantly higher than that in the adjacent normal myometrium throughout the menstrual cycle. In monolayer cultures of leiomyoma cells, the addition of either E2 (10 ng/mL) or P4 (100 ng/mL) resulted in an increase in PCNA expression in the cells compared to that in control cultures, whereas in monolayer cultures of myometrial cells, the addition of E2 augmented PCNA expression in the cells, but P4 did not. Immunoblot analysis of proteins extracted from cultured leiomyoma cells revealed that leiomyoma cells contained immunoreactive EGF with a molecular mass of 133 kDa and that the addition of P4 resulted in a remarkable increase in the expression of 133- and 71-kDa immunoreactive EGF in the cells compared to that in control cultures, whereas the addition of E2 resulted in a somewhat lower expression of immunoreactive EGF in the cells. Furthermore, immunocytochemical analysis with a monoclonal antibody to human EGF-R demonstrated that the treatment with E2 augmented EGF-R expression in the cells compared to that in untreated cells, but P4 did not. The concentrations of sex steroids used were within the physiological tissue concentrations found in leiomyomas and myometria. These results indicate that P4 up-regulates the expression of PCNA and immunoreactive EGF in leiomyoma cells, whereas E2 up-regulates the expression of PCNA and EGF-R in those cells. As it is evident that EGF plays a crucial role as a local factor in regulating leiomyoma growth, the P4-induced increase in PCNA expression in leiomyoma cells may be mediated by P4-induced enhanced expression of EGF-like proteins in the cells, whereas the E2-induced increase in PCNA expression in leiomyoma cells may be mediated by E2-induced enhanced expression of EGF-R in those cells. It is, therefore, conceivable that P4 and E2 act in combination to stimulate the proliferative potential of leiomyoma cells through the induction of EGF-like proteins and EGF-R expression in uterine leiomyoma.

Adult↗