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M Irahara

Publications and source records attributed to M Irahara.

At least 19 recordsLinked to original sources
PubMed1999

Glucocorticoid receptor-mediated post-ceramide inhibition of the interleukin-1beta-dependent induction of ovarian prostaglandin endoperoxide synthase-2 in rats.

Ovulation may constitute a cyclic, inflammatory-like process, wherein interleukin (IL)-1 induction and increased biosynthesis of prostanoids may feature prominently. In excess, glucocorticoids, potent anti-inflammatory agents, may exert an antiovulatory effect. This paper addresses the possibility that the antiovulatory action of glucocorticoids may be partly due to interference with ovarian prostanoid biosynthesis. Specifically, we examined the effect of treatment with dexamethasone, a synthetic glucocorticoid, on the IL-1-induced expression and activity of ovarian prostaglandin endoperoxide synthase (PGS)-2, the inducible variety of the rate-limiting enzyme in the prostaglandin cascade. Treatment of cultured whole ovarian dispersates from immature rats with dexamethasone for 48 h produced a significant decrease (98.9% inhibition) in the IL-1-supported expression of PGS-2 transcripts. Comparably marked inhibition was also noted for the corresponding immunoreactive protein. The dexamethasone effect was not limited to the IL-1-mediated induction of PGS-2 transcripts, comparable suppression being noted for the IL-1-mediated up-regulation of ovarian transcripts corresponding to IL-1beta, the IL-1 receptor antagonist, and the type I IL-1 receptor. The order of potency of the glucocorticoids studied was dexamethasone > prednisolone = cortisol. Dexamethasone proved equally effective in suppressing the induction of PGS-2 transcripts by congeners of the sphingomyelin-ceramide cycle (e.g., C-2 ceramide, sphingomyelinase, and sphingosine). The dexamethasone effect proved glucocorticoid-specific, as synthetic agonists representative of the progestin (R-5020), androgen (R-1881), and estrogen (diethylstilbestrol) steroid series proved to be without effect. Cotreatment with RU-486 resulted in reversal of the ability of dexamethasone to suppress PGS-2 activity or expression. Taken together, these observations suggest that dexamethasone is capable of glucocorticoid receptor-mediated/post-ceramide suppression of IL-1-supported ovarian PGS-2 transcript, protein, and activity. These findings are compatible with the view that the chronic anovulatory state associated with adrenal hyperactivity or glucocorticoid excess may be due in part to inhibition of ovarian prostaglandin biosynthesis.

Animals↗
PubMed1999

Ovarian interleukin-1 receptor antagonist in rats: gene expression, cellular localization, cyclic variation, and hormonal regulation of a potential determinant of interleukin-1 action.

It is hypothesized that the intraovarian interleukin (IL)-1 system plays a prominent role in the regulation of follicular development and ovulation. A central component of the intraovarian IL-1 system is the IL-1 receptor antagonist (IL-1RA), a protein acting as a pure IL-1 receptor antagonist and one for which intracellular (icIL-1RA) and secretory (sIL-1RA) varieties have been described. It was the objective of this study to explore rat ovarian IL-1RA gene expression, to establish the identity and relative abundance of its alternative transcripts, to study its cellular localization, to determine its cyclic variation, and to assess its hormonal regulation. Protected IL-1RA cDNA fragments corresponding to either sIL-1RA or icIL-1RA were barely detectable in untreated whole ovarian tissue of immature rat origin. However, sIL-1RA transcripts reached a maximal value (3.3-fold increase over untreated control values; p < 0.05) 12 h after hCG administration (time of projected ovulation). In situ hybridization localized IL-1RA to mural, antral, and cumulus granulosa cells. Modestly intense staining was also apparent in oocytes. The basal pattern of sIL-1RA expression by cultured whole ovarian dispersates was characterized by a spontaneous increase to a peak value at 4 h. The early (4 h) sIL-1RA burst proved IL-1-, nitric oxide-, and protein biosynthesis-independent. However, treatment with IL-1beta led to a secondary sIL-1RA peak at 48 h, an effect that was substantially reversed by IL-1RA. This stimulatory effect of IL-1beta on IL-1RA expression proved relatively specific, and nitric oxide independent, but contingent upon de novo protein biosynthesis. The in vitro expression of icIL-1RA was barely detectable. Taken together, these in vivo and in vitro observations 1) document the rat ovary as a site of IL-1RA (sIL-1RA > cIL-1RA) expression, 2) localize the relevant transcripts to the granulosa cell, 3) disclose peak expression at the time of ovulation, and 4) establish IL-1 dependence.

Animals↗
PubMed1999

Effects of activin on hormone secretion by single female rat pituitary cells: analysis by cell immunoblot assay.

We investigated the effect of activin A on secretion of LH, FSH, and prolactin (PRL) by female cultured rat pituitary cells at the single-cell level by means of the cell immunoblot assay. Anterior pituitary cells from 8-week-old female rats were preincubated with or without activin A for 24 h, after which they were monodispersed and immediately used for cell immunoblot assay. The percentages of LH-, FSH- and PRL-immunoreactive cell blots detected were 5.5, 5.3 and 43.1%, respectively, of all pituitary cells applied to the transfer membrane. The percentage of LH-secreting cells and mean LH secretion per cell did not change after treatment with activin. In contrast, activin significantly increased the percentage of FSH-secreting cells and mean FSH secretion per cell to 136.0 and 114. 5% respectively. In addition, activin significantly decreased the percentage of PRL-secreting cells and mean PRL secretion per cell to 52.2 and 72.0% respectively. These results suggest that (1) activin A has effects on female rat pituitary cells that increase not only the amount of FSH secretion per cell but also the number of FSH-secreting cells, and (2) activin A decreases both the amount of PRL secretion per cell and the number of PRL-secreting cells.

Activins↗
PubMed1998

The influence of ovariectomy on ob gene expression in rats.

Ovarian steroid hormones exert major influences on eating behaviour and body weight regulation of female rats. Ovariectomy (OVX) results in an increase in food intake and a concomitant increase in body weight, while estradiol (E2) replacement reverses these effects. In this study, we examined the influence of OVX on obese (ob) gene expression in rat adipose tissues and serum leptin concentration. Female Wistar rats, 10 weeks old, were divided into three groups: sham-operated control rats receiving corn oil (group 1, n = 4), ovariectomized rats receiving corn oil (group 2, n = 5), and ovariectomized rats receiving 17beta-E2 (10 microg/kg/day) replacement (group 3, n = 4). After 4 weeks, the rats and food consumption were weighed and serum E2 and leptin levels were measured by radioimmunoassays. Furthermore, the expression levels of ob mRNA obtained from the bilateral perimetric fat pads were estimated by Northern blot analysis. The mean weight and food consumption in group 2 were significantly (p < 0.01) heavier than those in group 1. But there were no significant differences between group 1 and group 3. The expression levels of ob mRNA in group 2 were lower than those in group 1, however, the levels of group 3 were restored to the level of group 1. On the other hand, no significant differences among the 3 groups as to serum levels of leptin were observed. The data herein clearly indicate that ovarian steroid hormones may be one of the factors involved in the regulation of ob gene.

Adipose Tissue↗
PubMed1998

Autoantibody against testosterone in a woman with hypergonadotropic hypogonadism.

We demonstrate that antitestosterone autoantibody is produced in a 24-yr-old woman with hypergonadotropic hypogonadism. The serum testosterone level measured by RIA was extremely elevated (5.80 ng/mL); after elution, serum testosterone had returned to a normal female value (0.21 ng/mL). The clinical features were suggestive of no androgen activity. Primary follicles were present in the patent's ovary. After gonadotropin treatment, conception was achieved, and a normal female infant was delivered. A gel filtration study showed that the testosterone-binding activity was eluted at the position of 15,000-kDa Ig. Scatchard analysis revealed a low affinity antibody; the association constant was 0.034 x 10(3) mol-1, and the maximal binding capacity was 162 mumol/mL. An immunoprecipitation study the chain-specific antibodies showed that the antitestosterone autoantibody belonged to kappa-type IgG. This subject is the first reported case with an endocrine disorder who possessed autoantibodies against testosterone.

Adult↗
PubMed1998

The endogenous feeding suppressant, 2-buten-4-olide, impairs the pulsatile secretion of luteinizing hormone through endogenous opioid peptides.

OBJECTIVE: To clarify the mechanism of the suppressive effect of 2-buten-4-olide (2-B4O), an endogenous feeding suppressant, on the pulsatile secretion of luteinizing hormone (LH), by studying whether endogenous opioid peptides are involved in this suppressive effect. METHODS: Using ovariectomized (ovx) rats, blood samples were taken every 6 min for 2 h after administration of 2-B4O or saline into the third cerebroventricle (3V) and sequential i.v. injection of naloxone (0. 5 mg/kg per h) or saline. Rats were divided into three experimental groups: group 1: 3V saline + i.v. saline (control); group 2: 3V 2-B4O + i.v. saline; group 3: 3V 2-B4O + i.v. naloxone. Serum LH concentrations were determined by double-antibody RIA. To determine whether 2-B4O affected the biosynthetic activity of the opioidergic neurons within the ovx rat arcuate nucleus, we measured the concentrations of pro-opiomelanocortin (POMC) mRNA, a precursor of beta-endorphin, in the rostral arcuate nucleus using non-radioactive in situ hybridization and a computerized image-analysis system. RESULTS: 2-B4O significantly suppressed the pulse frequency of LH (group 2: 1.5+/-0.33 pulses/2 h, group 1: 2.43+/-0.2 pulses/2 h; P < 0.05), but naloxone blocked its suppressive effect and restored the pulse frequency (group 3: 3.29+/-0.36 pulses/2 h, group 2: 1.5+/-0.33 pulses/2 h: P < 0.01). There were no significant changes in the mean LH concentrations and amplitude. Furthermore, 2-B4O significantly stimulated the expression of POMC mRNA in the rostral arcuate nucleus. CONCLUSION: These results suggest that 2-B4O may impair the pulsatile secretion of LH by activating the opioid pathway within the hypothalamus.

4-Butyrolactone↗
PubMed1997

Increase of mouse leptin production by adipose tissue after midpregnancy: gestational profile of serum leptin concentration.

The serum concentration of leptin in 10 week old virgin ICR mice assessed by RIA was 1.70 +/- 0.08 ng/ml. The serum leptin concentration in the pregnant mice mated at 10 weeks of age significantly increased from day 11 of pregnancy and reached a peak on day 17 of pregnancy (42.2 +/- 4.8 ng/ml). AFter the delivery, the serum leptin concentration rapidly decreased and reached the level of the virgin mouse on the seventh day in the puerperium. Tissue contents of leptin in the placenta, the decidua, the uterus, and the adipose tissue were between 40 to 130 ng/g wet tissue. However, leptin mRNA was expressed only in the adipose tissue and the level of leptin mRNA on days 13 and 17 of pregnancy increased 3- to 5-fold compared with that of virgin mouse. Tissue content of leptin in the adipose tissue significantly increased from day 17 of pregnancy compared with that of the virgin mouse. The m-leptin secretion from the adipose tissue also significantly increased in vitro. These results suggest that leptin, which was secreted by adipose tissue, may play important roles in mouse reproduction after midpregnancy.

Adipose Tissue↗
PubMed1997

Immunoreactive growth hormone-releasing hormone (IR-GHRH) in the feto-placental circulation and differential effects of L-dopa, L-arginine and somatostatin-14 on the plasma levels of IR-GHRH in normal adults.

The relation of the physiological releases of growth hormone-releasing hormone (GHRH) and growth hormone (GH) into the circulation in various conditions was investigated using a sensitive and specific radioimmunoassay for plasma GHRH. The mean fasting plasma level of immunoreactive (IR)-GHRH in 72 normal adults was 10.3 +/- 0.5 (mean +/- SEM) pg/ml and there was no significant sex difference in the level. The concentrations of IR-GHRH in plasma from the umbilical artery and umbilical vein were 107.3 +/- 20.5 pg/ml and 33.6 +/- 3.8 pg/ml, respectively, and a marked arterio-venous gradient was observed in all 12 individuals examined. The plasma level of IR-GHRH in the maternal vein was significantly lower than that in the cord blood, but was similar to that in non-pregnant women. In normal adults, although there was no apparent fluctuation in the level of plasma IR-GHRH or of plasma GH during bed rest, a significant increase of plasma IR-GHRH was detected followed by, or synchronized with the surge of plasma GH after oral administration of L-dopa. In contrast, on L-arginine infusion, no proportional elevation of plasma IR-GHRH with increase in plasma GH was observed. During and after intravenous infusion of somatostatin, the circulating IR-GHRH level did not increase, but on stopping the infusion there was an immediate and marked rebound surge of GH. We conclude that 1) the elevated IR-GHRH in the cord blood plasma originates from the fetus and may have a primary role in enhancing secretion of GH which promotes growth in early human life, and 2) the participations of GHRH in the mechanisms of GH secretion seen after administrations of L-dopa, L-arginine and somatostatin are different.

Adult↗
PubMed1997

Effects of transforming growth factor-beta on the production of parathyroid hormone-related peptide in a human ovarian cancer cell line in vitro.

OBJECTIVE: We examined the effects of transforming growth factor-beta 1 (TGF-beta 1) on intracellular parathyroid hormone-related peptide (PTHrP) production in a human ovarian cancer cell line (HOC-21). METHODS: Various concentrations of TGF-beta 1 were added to a culture medium, and the numbers of cells were counted. HOC-21 cells were cultured with or without TGF-beta 1, and intracellular PTHrP was measured by a radioimmunoassay kit that recognized the carboxy-terminal protein while counting the number of cells. Furthermore, a 125I-TGF-beta 1 binding assay was carried out. Values were analyzed statistically using an analysis of variance followed by an unpaired t-test. RESULTS: Five ng/ml of TGF-beta 1 inhibited the cell growth on Day 1 after plating. The TGF-beta 1 significantly (p < 0.05) stimulated intracellular PTHrP production in a time-dependent manner, also by Day 1. A 125I-TGF-beta 1 binding study revealed that HOC-21 cells expressed a high affinity for the TGF-beta 1 receptor. CONCLUSION: The suppression of human ovarian cancer cell proliferation by TGF-beta 1 might be involved in the production of PTHrP.

Cell Division↗
PubMed1997

Measurement of N- and C-terminal-region fragments of parathyroid hormone-related peptide in milk from lactating women and investigation of the relationship of their concentrations to calcium in milk.

Parathyroid hormone-related peptide (PTHrP) is found in very high concentrations in the milk of various mammals. However, little is known about its physiological role in this fluid. To obtain detailed profiles of PTHrP in milk, we measured the concentrations of PTHrP in human milk by two different region-specific assays, PTHrP(1-87) (N-PTHrP) and PTHrP(109-141) (C-PTHrP). We also examined the correlations between PTHrP and Ca concentrations in milk as well as the correlations between PTHrP and secreted milk volume. The levels of N-PTHrP and C-PTHrP were relatively low after delivery and gradually increased to 13.87 +/- 2.40 nmol/l (mean +/- S.E.M.) and 56.39 +/- 11.31 nmol/l respectively on the 10th day postpartum. N-PTHrP concentration remained steady until the 6th month postpartum when weaning starts, at which point it decreased slightly. C-PTHrP levels changed in a similar way to N-PTHrP levels but were 2- to 5-fold higher. Milk Ca concentration, and content, correlated with C-PTHrP concentration, and content (r = 0.422 and r = 0.769 respectively; P < 0.0001) but not with N-PTHrP. N-PTHrP concentration in the milk samples on the 4th day postpartum correlated with the volume of milk secreted during the 24 h before the samples were taken (r = 0.524, P < 0.01), but C-PTHrP concentration did not. These results suggest that PTHrP in human milk may play some role in the maintenance of lactation through the N-terminal region and in promoting Ca transfer into milk via the C-terminal region.

Calcium↗
PubMed1997

[TRH test].

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Anorexia Nervosa↗
PubMed1997

Immunological functions of adult T cell leukemia cells of a patient complicated with synchronous double primary gynecologic cancer.

A patient with triple malignancies is reported, who presented cervical cancer, vulvar cancer and adult T cell leukemia (ATL). ATL was diagnosed as a smouldering type, because antibody to human T cell leukemia virus associated antigen (ATLA) was positive with a titer of 1:160. Although her malignant cells had an OKT 4+8-3+Tac+ phenotype, the cells did not display helper T cell functions. Namely they showed no response to Phytohemagglutinin (PHA) and Interleukin 2 (IL-2) and suppressed the PWM driven IgG synthesis of B cells obtained from healthy donor. They did not produce IL-2 by stimulation with PHA and phorbol myristate acetate (PMA). Furthermore, these ATL cells were producing IL-2 inhibitor like factors. As synchronous triple malignancies are extremely rare, two gynecologic cancers seem to ascribe to the suppressing state of the immunosurveillance mechanism by viral infection.

Aged↗
PubMed1997

[Estrogen, progesterone--biosynthesis, receptor and action].

Ovarian sex steroid hormones, estrogen and progesterone, have crucial effects on female reproductive functions such as the development and maturation of reproductive organs and the appearance of normal menstrual cycles. The precursor of steroid hormones is a cholesterol that is synthesized de novo from acetate or that is taken in as LDL-cholesterol via LDL-receptor. Members of cytochrome P450 superfamily and hydroxysteroid dehydrogenase (HSD) involved in the biosynthesis of the steroid hormones. In the corpus luteum, P450scc and 3 beta-HSD catalyze the pathway from cholesterol to progesterone and in the granulosa cells, P450arom (aromatase) and two HSDs catalyze the biosynthesis of estrogen from C19 steroid synthesized in the theca cells having P450(17) alpha. In the target cell, steroid binds to and activates its receptor located primarily in the nucleus. Binding of ligand results in dimerization of the receptor due to its conformational change. The steroid-receptor complex binds to specific hormone responsive element of the target gene at the site of DNA binding region and then activates transcription of the gene. Main action of estrogen is to stimulate the proliferation and development of cells due to enhancement of the synthesis of specific DNAs and proteins in the female reproductive organs. Progesterone regulates the action of estrogen through the decrease of estrogen receptor and down regulation of its own receptor.

Estrogens↗
PubMed1997

[Physiology and action of prolactin].

Prolactin (PRL) is a peptide hormone secreted by the lactotroph of the anterior pituitary. Secretion of PRL is regulated negatively by hypothalamic hormone. Dopamine is the major physiologic prolactin inhibiting factor (PIF). PRFs as TRH, VIP and oxytosin have prolactin releasing activity. Prolactin secretion is induced by sleep, stress, sexual intercourse and suckling stimulus. Serum level of PRL is increased by estrogen. Therefore, PRL level is higher in women, especially in the late follicular phase and during pregnancy. Lactation is the major biologic function of PRL in humans and essential to reproduction. Other function of PRL, such as regulation of ovarian function, osmoregulation and immunoregulation is not fully established. Many action of PRL remained to be clarified.

Adolescent↗
PubMed1996

Effect of IL-1 in amniotic fluid on the fetal keratinocyte.

IL-1 alpha is predominantly increased in amniotic fluid of the patients with premature rupture of the membrane (PROM). In the present study we examined the effect of IL-1 on the fetal keratinocytes, one of the main tissue exposed to the increased IL-1. Exposure of IL-1 at over 0.1 pg/ml IL-1 significantly (p < 0.01) inhibited proliferation of the keratinocytes in low calcium keratinocyte growth medium obtained from the umbilical cord. Immunohistochemical analysis using antibodies to various cytokeratins revealed that the umbilical cord keratinocytes is more similar to the mucosal epithelium than the skin epithelium. These results suggest that IL-1 alpha increased in amniotic fluid in the PROM cases leads the immature proliferating mucosal epithelium to maturate for protection of the fetus against environment.

Amniotic Fluid↗