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N Sugino

Publications and source records attributed to N Sugino.

At least 19 recordsLinked to original sources

Expression of vascular endothelial growth factor (VEGF) and its receptors in human endometrium throughout the menstrual cycle and in early pregnancy.

Immunohistochemistry for vascular endothelial growth factor (VEGF) and its receptors, fms-like tyrosine kinase (flt-1) and kinase insert domain-containing region (KDR), was performed on human endometrium obtained from patients with normal menstrual cycles, patients given oestrogen and progesterone, and women in early pregnancy. Intense immunostaining of VEGF was observed in both glandular epithelial and stromal cells during the mid-secretory phase; the immunostaining intensity was increased by administration of oestrogen plus progesterone and strong immunostaining was observed in decidual cells of early pregnancy. In addition to the immunostaining in vascular endothelial cells, strong KDR immunostaining was observed in glandular epithelial cells and in decidualized stromal cells induced by administration of oestrogen plus progesterone, whereas flt-1 immunostaining was negligible. Strong immunostaining for flt-1 and KDR was found in both vascular endothelial cells and decidual cells in early pregnancy. Endometrial stromal cells isolated from proliferative phase endometrium were incubated with oestrogen (10(-8) mol l-1) and medroxyprogesterone acetate (MPA; 10(-6) mol l-1) for 18 days to study the regulation of VEGF, flt-1 and KDR in endometrial stromal cells by oestrogen and progesterone. Expression of VEGF and KDR mRNAs was increased significantly by oestrogen and MPA, accompanied by decidualization, whereas flt-1 mRNA expression was not affected. In conclusion, VEGF and its receptors may play important roles in implantation and maintenance of pregnancy.

Adult↗

A case of 46,X,der(X)(pter-->q21::p21-->pter) with gonadal dysgenesis, tall stature, and endometriosis.

OBJECTIVE: To report a case of 46,X,der(X)(pter-->q21::p21-->pter) with gonadal dysgenesis, tall stature, and endometriosis. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 20-year-old primary amenorrheal woman receiving estrogen-progestogen substitution. INTERVENTION(S): G-banding, comparative genomic hybridization, fluorescence in situ hybridization (FISH), and laparoscopy. MAIN OUTCOME MEASURE(S): A recombinant X chromosome, 46,X,der(X)(pter-->q21::p21-->pter), and pelvic endometriosis. RESULT(S): The patient's chromosomal abnormality was misjudged by the use of G-banding as a distal part deletion of the long arm in one X chromosome. Comparative genomic hybridization and fluorescence in situ hybridization analyses with locus-specific probes revealed 46,X,der(X)(pter-->q21::p21-->pter). The laparoscopic examination showed bilateral streak gonads and blue berry spots at the pelvic peritoneum, which were confirmed by evaluation of biopsy specimens. CONCLUSION(S): Recent advances of genetic strategies make it easy to determine karyotype and phenotype abnormalities. We have to keep our mind on the potential of endometriosis with patients who are receiving estrogen-progestogen substitution.

Adult↗

Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy.

Serum melatonin concentrations were studied in normal pregnant women and in women with several types of pathologic pregnancies, e.g., twins, preeclampsia or intrauterine growth retardation (IUGR). Blood samples were collected from the maternal antecubital vein at 14:00 hr (daytime) and 02:00 hr (nighttime) during pregnancy, and also from the umbilical vein and artery immediately after delivery. Serum melatonin concentrations were measured by radioimmunoassay. Daytime serum melatonin levels in normal (single fetus; singleton) pregnancies were low. While the levels showed an increasing tendency toward the end of pregnancy, no statistically significant changes occurred. On the other hand, the nighttime serum melatonin levels increased after 24 weeks of gestation, with significantly (P < 0.01) high levels after 32 weeks; these values decreased to non-pregnant levels on the 2nd day of puerperium. Nighttime serum melatonin levels were significantly (P < 0.05) higher in twin pregnancies after 28 weeks of gestation than in singleton pregnancies, whereas the patients with severe preeclampsia showed significantly (P < 0.05) lower serum melatonin levels than the mild preeclampsia or the normal pregnant women after 32 weeks of gestation. Melatonin concentrations in umbilical vessels showed a higher tendency in neonates who were born during at night compared with the other neonates; moreover, those in the umbilical artery were generally higher than those in the umbilical vein. The present results indicate that in humans, the maternal serum melatonin levels show a diurnal rhythm, which increases until the end of pregnancy, reflecting some pathologic states of the feto-placental unit. Fetuses may produce melatonin with a circadian rhythm.

Adult↗

Reactive oxygen species stimulate prostaglandin F2 alpha production in human endometrial stromal cells in vitro.

BACKGROUND: The present study was undertaken to investigate the effect of reactive oxygen species on prostaglandin F2 alpha (PGF2 alpha) production by human endometrial stromal cells (ESC). METHODS AND RESULTS: Isolated ESC were incubated with hydrogen peroxide, which induces lipid peroxidation. Hydrogen peroxide increased both intracellular and medium concentrations of PGF2 alpha (P < 0.01). A time course study showed that hydrogen peroxide significantly increased PGF2 alpha concentrations in the medium after 6 h incubation (P < 0.01), after which no further increase was observed. To study whether the increase in PGF2 alpha production caused by hydrogen peroxide was mediated by cyclooxygenase, ESC were incubated with indomethacin (0.5 microg/ml), an inhibitor of cyclooxygenase, in the presence of hydrogen peroxide. Indomethacin significantly blocked the increases in PGF2 alpha production caused by hydrogen peroxide (P < 0.01). Hydrogen peroxide also increased PGF2 alpha production by decidualized ESC (P < 0.01), induced by the incubation with medroxyprogesterone acetate (10(-6) mol/l) and oestradiol (10(-8) mol/l). CONCLUSIONS: Reactive oxygen species stimulate PGF2 alpha production in ESC, suggesting that they might influence endometrial function by regulating PGF2 alpha production.

Adult↗

Induction of manganese superoxide dismutase by tumour necrosis factor-alpha in human endometrial stromal cells.

The present study was undertaken to investigate the effect of tumour necrosis factor-alpha (TNFalpha) on superoxide dismutase (SOD) expression in human endometrial stromal cells (ESC) and to determine whether there is a difference in responsiveness to TNFalpha between ESC and decidualized ESC. TNFalpha increased manganese-SOD (Mn-SOD) mRNA level and Mn-SOD activity in a dose-dependent manner in ESC. The concentration of TNFalpha required for an effect was lower for decidualized ESC than for non-decidualized ESC. TNFalpha had no effect on copper-zinc-SOD (Cu,Zn-SOD) expression in either type of cell. Incubation of ESC with actinomycin D, an RNA synthesis inhibitor, blocked TNFalpha-induced Mn-SOD mRNA expression, but cycloheximide, a protein synthesis inhibitor, had no effect. H7, an inhibitor of protein kinase C (PKC), also inhibited TNFalpha-stimulated Mn-SOD mRNA expression in both types of cells. These findings suggest that TNFalpha-induced Mn-SOD expression is regulated at the transcription level and mediated by PKC-dependent phosphorylation and that de-novo protein synthesis is not required for the TNFalpha effect. In summary, TNFalpha induces Mn-SOD expression in human ESC. This phenomenon may be important for protection of ESC from cytokine-mediated oxidative stress.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Regulation and role of vascular endothelial growth factor in the corpus luteum during mid-pregnancy in rats.

The present study was undertaken to investigate the role of vascular endothelial growth factor (VEGF) in luteal angiogenesis and the regulation of VEGF in the corpus luteum (CL) during mid-pregnancy in rats. Protein concentrations and mRNA levels of VEGF in the CL significantly increased from Day 9 to Day 12 and remained at the same level as Day 12 until Day 15. To study whether estradiol is involved in VEGF expression between Day 12 and Day 15, rats undergoing hypophysectomy-hysterectomy on Day 12 were treated with estradiol until Day 15. Protein concentrations and mRNA levels of VEGF in the CL were significantly decreased by hypophysectomy-hysterectomy, and this inhibitory effect was completely reversed by estradiol treatment. Changes in vascular density in the CL were parallel to those in VEGF expression. To examine whether the effect of estradiol is mediated by VEGF, anti-VEGF antibody was administered to hypophysectomized-hysterectomized rats simultaneously with estradiol. The recovery in the vascular density, CL weight, and serum progesterone concentration caused by estradiol was significantly inhibited by the anti-VEGF antibody treatment. In conclusion, the present study has demonstrated that VEGF contributes to luteal angiogenesis, CL development, and progesterone production during mid-pregnancy in rats and that luteal VEGF expression is increased by estradiol.

Animals↗

Prenatal influence of ischemia-hypoxia-induced intrauterine growth retardation on brain development and behavioral activity in rats.

The effects of intrauterine growth retardation (IUGR) on brain histological or functional development were examined in rats. IUGR was induced by ligating the bilateral uterine arteries at day 17 of pregnancy. On day 22 of pregnancy, cesarean section was performed, and pups with a birth weight of <2 SD of the mean birth weight of control pups were regarded as IUGR rats. Morphological changes of the brain were studied by Nissl's staining at different timepoints during prenatal and postnatal periods. For behavioral study, an open-field test was performed at 5, 7 and 10 weeks after birth. Histological studies showed the migration disorder of the neurons in the cerebral cortex from embryonic day 17 to postnatal day (PD) 49. The open-field test revealed locomotor disturbance at PD49 in male IUGR rats, but not in female IUGR rats or control rats. It is concluded that IUGR due to antenatal ischemia-hypoxia causes morphological changes in the central nervous system, and induces behavioral impairment, particularly in male rats.

Animals↗

Urocortin and corticotropin-releasing factor receptor expression in normal cycling human ovaries.

Urocortin is a member of the CRF neuropeptide family and has a 43% homology to CRF in amino acid sequence. Urocortin has been found to bind with high affinity to CRF receptors. CRF has been detected in the human ovary and has been demonstrated to suppress ovarian steroidogenesis in vitro. In this study we examined urocortin and CRF receptor expression in normal cycling human ovaries, using immunohistochemistry and RT-PCR. Normal cycling human ovaries were obtained at oophorectomy and hysterectomy from patients who underwent surgery for cervical cancer or myoma uteri. Intense urocortin immunoreactivity was detected in luteinized thecal cells of regressing corpora lutea, in which only luteinized thecal cells have the capacity for steroidogenesis. Immunoreactive urocortin was also detected in luteinized granulosa and thecal cells of functioning corpora lutea, in which both cell components are capable of producing steroids. RT-PCR analyses revealed that messenger ribonucleic acid levels for urocortin, CRF, and CRF receptor type 1 and type 2alpha were significantly higher in the regressing corpus luteum than in the functioning corpus luteum. The spatial and temporal immunolocalization patterns of CRF receptor were similar to those of urocortin. These results suggest that urocortin is locally synthesized in steroidogenic luteal cells and acts on them as an autocrine and/or paracrine regulator of ovarian steroidogenesis, especially during luteal regression.

Adult↗

Expression of vascular endothelial growth factor (VEGF) receptors in rat corpus luteum: regulation by oestradiol during mid-pregnancy.

The aim of this study was to investigate the expression of vascular endothelial growth factor (VEGF) receptors, the fms-like tyrosine kinase (flt-1) and kinase insert domain-containing region (KDR), in corpora lutea obtained at different stages of the oestrous cycle and during pregnancy in rats. Immunohistochemistry revealed that both flt-1 and KDR were localized in luteal cells in addition to vascular endothelial cells, and that the intensity of staining was stronger in pregnant rats than in cyclic rats. Rats undergoing hypophysectomy-hysterectomy on day 12 of pregnancy were treated with oestradiol until day 15 of pregnancy to determine whether oestradiol is involved in expression of flt-1 and KDR mRNA in the corpus luteum during mid-pregnancy. The flt-1 and KDR mRNA contents in the corpus luteum were decreased significantly by hypophysectomy-hysterectomy, and these decreases recovered significantly after oestradiol treatment. Changes in the mass of the corpus luteum and serum progesterone concentrations paralleled the changes in expression of flt-1 and KDR mRNA. Developmental studies indicated that flt-1 and KDR mRNA contents in the corpus luteum were constant until day 15 of pregnancy but decreased significantly on day 21 of pregnancy. In conclusion, both flt-1 and KDR were expressed in luteal cells in addition to vascular endothelial cells, and expression was upregulated by oestradiol during mid-pregnancy. flt-1 and KDR may play a role in development of the corpus luteum and in production of progesterone during mid-pregnancy in rats.

Animals↗

Superoxide dismutase expression in the human corpus luteum during the menstrual cycle and in early pregnancy.

To investigate the possible role of the superoxide radical and its scavenging system in the human corpus luteum, superoxide dismutase (SOD) values and lipid peroxide concentrations were analysed in the corpora lutea during the menstrual cycle and in early pregnancy. Copper-zinc SOD (Cu,Zn-SOD) activities increased from the early to mid-luteal phase, and gradually decreased thereafter and were the lowest in the regression phase. In pregnant corpus luteum, Cu,Zn-SOD activities were significantly higher than those in the mid-luteal phase. In contrast, manganese SOD (Mn-SOD) activities were low in the mid-luteal phase and increased toward the regression phase. Changes in mRNA expression of both types of SOD were similar to changes in their activities. Lipid peroxide concentrations were the highest in the regression phase whereas they were remarkably low in pregnant corpus luteum. The effects of human chorionic gonadotrophin (HCG) on luteal SOD were studied in vitro. HCG significantly increased Cu,Zn-SOD expression in mid-luteal phase corpora lutea, but not in late luteal phase corpora lutea. In conclusion, the present study suggests that the superoxide radical and its scavenging system, especially Cu,Zn-SOD, play important roles in the regulation of human luteal function. The stimulation of luteal Cu, Zn-SOD expression by HCG may be important in maintaining luteal cell integrity when pregnancy occurs.

Adult↗

Induction of superoxide dismutase by decidualization in human endometrial stromal cells.

The present study was undertaken to investigate the effect of decidualization on superoxide dismutase (SOD) expression in human endometrial stromal cells (ESC). To induce decidualization, isolated ESC were incubated with medroxyprogesterone acetate (MPA, 10(-6) mol/l) and oestradiol (10(-8) mol/l) for 23 days. Insulin-like growth factor-binding protein-1 (IGFBP-1) was used as a marker of decidualization. SOD mRNA in ESC was significantly increased on day 12 of the hormone treatment (P < 0.01), which was concomitant with the onset of IGFBP-1 mRNA expression, and further increased until day 23 of the treatment in a manner similar to the change in IGFBP-1 expression. To examine the synergistic effect of human chorionic gonadotrophin (HCG) with MPA and oestradiol on SOD and IGFBP-1 expression, ESC were incubated with HCG in the presence or absence of MPA and oestradiol. HCG had no synergistic effect on SOD and IGFBP-1 expression. SOD activities in the decidualized endometrial tissue obtained from patients given oestradiol and progesterone for 7-10 days were significantly higher than those in the non-decidualized endometrial tissue from patients without the hormone treatment (P < 0.01). In conclusion, SOD expression in ESC was induced by MPA and oestradiol accompanied by decidualization, suggesting that SOD may play important roles in decidualization of ESC.

Adult↗

Decreased superoxide dismutase expression and increased concentrations of lipid peroxide and prostaglandin F(2alpha) in the decidua of failed pregnancy.

To study the possible role of the superoxide radical and its scavenging system in the decidua of early pregnancy, superoxide dismutase (SOD) values and concentrations of lipid peroxide and prostaglandin F(2alpha) (PGF(2alpha)) were analysed in the decidua obtained from normal pregnancy and failed pregnancy. Failed pregnancy was divided into two groups; spontaneous abortion with or without vaginal bleeding. In the spontaneous abortion with vaginal bleeding, total SOD activities, Cu,Zn-SOD activities and Cu,Zn-SOD mRNA values in the decidua were significantly lower, and concentrations of lipid peroxide and PGF(2alpha) were significantly higher, than those in the normal pregnancy and the spontaneous abortion without vaginal bleeding. In contrast, activities and mRNA values of Mn-SOD were significantly higher in the spontaneous abortion with vaginal bleeding than the other two groups. There was no significant difference in all of these parameters between the normal pregnancy and the spontaneous abortion without vaginal bleeding. In conclusion, the decrease in Cu,Zn-SOD expression and the increase in lipid peroxide in the decidua could be involved in the termination of spontaneous abortion, mediated through the increase in PGF(2alpha) synthesis. In other words, Cu,Zn-SOD may contribute to the maintenance of pregnancy by preventing the accumulation of superoxide radicals that cause PGF(2alpha) synthesis.

Abortion, Spontaneous↗

Rescue of the corpus luteum and an increase in luteal superoxide dismutase expression induced by placental luteotropins in the rat: action of testosterone without conversion to estrogen.

The superoxide radical and its scavenger, superoxide dismutase (SOD), play important roles in the regulation of corpus luteum function. The present study was undertaken to investigate whether SOD is related to pregnancy-induced maintenance of corpus luteum function. Placentae obtained from rats on Day 12 of pregnancy were incubated for 24 h, and the supernatant was used as placental luteotropins. Pseudopregnant rats were given the placental incubation medium from Day 9 to Day 12 of pseudopregnancy. The treatment significantly increased serum progesterone concentrations on Day 12 of pseudopregnancy. Both activities and mRNA levels of copper-zinc SOD (Cu,Zn-SOD) and manganese SOD (Mn-SOD) in the corpus luteum were also increased on Day 12 of pseudopregnancy. Treating the placental incubation medium with charcoal significantly eliminated the stimulatory effects of placental incubation medium on serum progesterone concentrations and luteal Mn-SOD expression, but not on Cu,Zn-SOD expression. The inhibitory effect of the charcoal treatment on luteal Mn-SOD expression was reversed by supplementation with testosterone or dihydrotestosterone (DHT), but serum progesterone concentrations were recovered only by DHT. Testosterone or DHT alone had no effect on serum progesterone concentrations and luteal SOD expression. In conclusion, placental luteotropins increased SOD expression in the corpus luteum and stimulated progesterone production, suggesting that SOD is involved in the maintenance of the corpus luteum function by placental luteotropins. In addition, androgen, with other placental luteotropins, acted to stimulate progesterone production and Mn-SOD expression in pseudopregnant rats.

Animals↗

Expression of vascular endothelial growth factor and its receptors in the human corpus luteum during the menstrual cycle and in early pregnancy.

To investigate the possible role of vascular endothelial growth factor (VEGF) and its receptors in the human corpus luteum (CL), expression of VEGF and its receptors, the fms-like tyrosine kinase and the kinase insert domain-containing region (KDR), was analyzed in the CL during the menstrual cycle and in early pregnancy. Immunohistochemistry revealed that VEGF was localized in luteal cells and both flt-1 and KDR were also localized in luteal cells, in addition to vascular endothelial cells. Messenger RNA (mRNA) expression of VEGF, flt-1, and KDR remained constant in the CL during the luteal phase and was lower in the regression phase. In the pregnant CL, VEGF mRNA expression was higher compared with that in the midluteal phase, and mRNA expression of both flt-1 and KDR was the same as that in the midluteal phase. Western blot analyses revealed that the change in protein expression of VEGF, flt-1, and KDR was similar to that in their mRNA expression. To study the effect of human CG (hCG) on VEGF expression in the CL, corpora lutea obtained from the midluteal phase were incubated with hCG (1 IU/ml) for 6 h. hCG increased the expression of mRNA and protein of VEGF. In conclusion, VEGF and its receptors may play important roles in development and function of the CL, and VEGF may exert a paracrine-autocrine role in regulating luteal function. hCG may act to prolong the life span of the CL by stimulating VEGF expression when pregnancy occurs.

Adult↗

Expression of Bcl-2 and Bax in the human corpus luteum during the menstrual cycle and in early pregnancy: regulation by human chorionic gonadotropin.

To investigate the relationship between apoptosis and the Bcl-2/ Bax system in the human corpus luteum (CL), the frequency of apoptosis and expression of Bcl-2 and Bax were examined in the CL during the menstrual cycle and in early pregnancy. In situ analysis of DNA fragmentation showed that the number of apoptotic cells was much greater in the regressing CL than that in the midluteal phase CL, whereas there were almost no apoptotic cells in the CL of early pregnancy. Immunohistochemistry revealed that Bcl-2 expression was observed in the luteal cells in the midluteal phase and early pregnancy, but not in the regressing CL. In contrast, Bax immunostaining was observed in the regressing CL, but not in the midluteal phase and early pregnancy. bcl-2 messenger ribonucleic acid (mRNA) levels in the CL during the menstrual cycle were highest in the midluteal phase and lowest in the regressing CL. In the CL of early pregnancy, bcl-2 mRNA levels were significantly higher than those in the midluteal phase. In contrast, bax mRNA levels were highest in the regressing CL and remarkably low in the CL of early pregnancy. Western blot analyses revealed that Bcl-2 expression was significantly lower in the regressing CL than in the midluteal phase and early pregnancy, and that Bax expression was, in contrast, significantly higher in the regressing CL than in the midluteal phase and was remarkably low in the CL of early pregnancy. When corpora lutea of the midluteal phase were incubated with hCG, hCG significantly increased the mRNA and protein levels of Bcl-2 and significantly decreased those of Bax. In conclusion, Bcl-2 and Bax may play important roles in the regulation of the life span of the human CL by controlling the rate of apoptosis. hCG may act to prolong the life span of the CL by increasing Bcl-2 expression and decreasing Bax expression when pregnancy occurs.

Adult↗

[Natriuresis and blood pressure in patients with chronic renal failure following L-arginine infusion].

Nitric oxide (NO) is known to be generated from L-arginine and may regulate glomerular filtration, tubular sodium reabsorption, and renin secretion. Impairment of renal function might influence NO production secondary to endothelial dysfunction, decreased NO synthesis and increased activity of arginine analogues inhibiting NO synthase. In this study, we evaluated the effect of L-arginine on the blood pressure and urinary sodium excretion in patients with chronic renal failure. A 300-ml dose of 10% L-arginine solution was administered intravenously over 30 min and blood pressure was monitored every 10 min under basal conditions and for 120 min after infusion. The patients were divided into two groups based on the reduction in mean blood pressure (dMBP) following infusion, namely non-responders (dMBP < 10 mmHg) and responders (dMBP > 10 mmHg). Urine and blood samples were collected to determine electrolytes, urinary NO2 + NO3 by the Griess method, urinary cGMP, plasma renin activity (PRA), and the plasma aldosterone concentration (PAC). L-arginine significantly decreased MBP in 8 patients and caused no significant change in 10 patients. Urinary sodium excretion and the NO2 + NO3 level were significantly increased following L-arginine infusion and the increment of fractional excretion of sodium was higher in responders. However, there were no significant changes in PRA, PAC, and cGMP. Our findings suggest that a vasodilator effect of NO induced by L-arginine loading may, at least in part, be associated with increased renal sodium excretion in patients with chronic renal failure.

Adult↗

Superoxide dismutase in normal cycling human ovaries: immunohistochemical localization and characterization.

OBJECTIVE: To investigate the expression of manganese (Mn) and copper-zinc (Cu,Zn) superoxide dismutase (SOD) in normal cycling human ovaries throughout the menstrual cycle. DESIGN: Descriptive, controlled study. SETTING: Tohoku University School of Medicine. PATIENT(S): Twenty-four normal cycling human ovaries were obtained from patients who underwent oophorectomy and hysterectomy for squamous cell carcinoma of the uterine cervix. INTERVENTION(S): Immunohistochemistry for Mn-SOD and Cu,Zn-SOD. MAIN OUTCOME MEASURE(S): Immunostaining. RESULT(S): In the follicular stage, Mn-SOD immunoreactivity was detected in granulosa and theca interna cells of steroid-producing follicles, that is, preantral, nondominant, dominant, and atretic follicles, whereas Cu,Zn-SOD was detected in theca interna cells of these follicles and in granulosa cells of dominant follicles. In the luteal stage, immunoreactivity for Mn-SOD and Cu,Zn-SOD was observed in both luteinized granulosa and theca cells of the functioning corpus luteum. In the early degenerating corpus luteum, both Mn-SOD and Cu,Zn-SOD were positive in steroid-producing luteinized theca cells. Mn-SOD immunoreactivity was also detected in nonsteroid-producing luteinized granulosa cells and macrophages. CONCLUSION(S): Our results suggest that the expression of Mn-SOD and Cu,Zn-SOD closely correlates with steroidogenesis in the human ovary. In addition, Mn-SOD may play an important role in the process of luteal regression.

Adult↗