Biomedical subjects

H Kogo

Publications and source records attributed to H Kogo.

At least 37 records · Page 2Linked to original sources

PubMed2000

Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae.

Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T(4)) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T(4) treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T(4) levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. The contractions induced by norepinephrine (NE) were significantly suppressed in aortic rings from rats treated with T(4) compared with control rats. N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), significantly enhanced NE-induced contraction in aortic rings from both control and T(4)-treated rats, and the enhancement was greater in rats treated with T(4) than control rats. The relaxations induced by either acetylcholine (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T(4) treatment. L-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T(4)-treated rats. L-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, but not with rats treated with T(4). T(4) treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascular responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amount of eNOS protein.

Acetylcholine↗

PubMed2000

Isoforms of caveolin-1 and caveolar structure.

The relationship between caveolin-1 isoforms alpha and beta and caveolar ultrastructure was studied. By immunofluorescence microscopy of human fibroblasts, caveolae were observed as dots positive for caveolin-1, but many dots labeled by an antibody recognizing both isoforms (anti-alphabeta) were not labeled by another antibody specific for the alpha isoform (anti-alpha). Immunogold electron microscopy of freeze-fracture replicas revealed caveolae of different depths, and indicated that anti-alpha labeled deep caveolae preferentially over shallow ones, whereas anti-alphabeta labeled both forms with an equivalent frequency and intensity. The presence of the beta isoform in deep caveolae was confirmed by labeling epitope-tagged beta-caveolin. When made to be expressed in HepG2 cells lacking endogenous caveolins, the alpha isoform formed caveolar depressions efficiently, but the beta isoform hardly did so. Caveolae were also formed in cells expressing the two isoforms, but their frequency was variable among cells of the same clone. Coexpression of caveolin-1 and caveolin-2 caused more efficient formation of deep caveolae than caveolin-1 alone. The result indicates that the two isoforms of caveolin-1 have a different potential for forming caveolae structure, and more importantly, that deep and shallow caveolae may be diversified in their molecular composition.

Adult↗

PubMed2000

Dexamethasone or triamcinolone increases follicular development in immature female rats.

We have previously reported that dexamethasone increased follicle-stimulating hormone (FSH) secretion via suppression of inhibin in immature female rats. In the present study, we investigated the effects of dexamethasone or triamcinolone on follicular development and ovarian functions (estradiol and inhibin secretion) in equine chorionic gonadotropin (eCG)-primed immature female rats. Dexamethasone significantly increased the number of ovulated oocytes in immature female rats treated with 5 i.u. eCG. Serum concentration of FSH in eCG-treated female rats was increased by administration of dexamethasone or triamcinolone, showing the peak value at 9 h after its administration, although the levels of inhibin markedly decreased at that time. Serum concentrations of inhibin and estradiol in eCG-treated female rats increased at 24 h after administration of dexamethasone or triamcinolone. These results demonstrate that dexamethasone or triamcinolone increases FSH secretion, and the excess amount of FSH strongly stimulates follicular development cooperating with exogenous eCG.

Animals↗

PubMed1999

Dexamethasone increases follicle-stimulating hormone secretion via suppression of inhibin in rats.

In the present study, the effects of dexamethasone on follicle-stimulating hormone (FSH) secretion in immature female rats were investigated. Dexamethasone increased the selective secretion of FSH and decreased plasma concentrations of inhibin in immature female rats. The effects of dexamethasone on FSH secretion were not confirmed in rats treated with ovariectomy or immunoneutralization against inhibin. In addition to the direct effect of dexamethasone on FSH synthesis in gonadotrophs, the present study has clearly demonstrated that the increased level of FSH in dexamethasone-treated rats is mediated by suppression of ovarian function, especially by the inhibition of inhibin secretion.

Animals↗

PubMed1999

Granulocyte-macrophage colony-stimulating factor enhances interleukin-1beta stimulated histamine release in the preovulatory rat ovary.

The existence of immune cells including macrophages and mast cells in rat ovary implies that various cytokines from these cells may play a role in ovarian functions. The aim of the present study was to investigate whether granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-1beta are capable of stimulating histamine release and steroidogenesis in rat ovary, and to determine the sites of histamine production in the ovary. Histamine release from preovulatory ovarian tissues was stimulated in a dose-dependent manner at 3-30 ng/ml of GM-CSF in the presence of interleukin-1beta (10 ng/ml). However, treatment with GM-CSF and interleukin-1beta did not cause any significant change in the levels of ovarian steroids. Intense staining of histidine decarboxylase in the ovary was immunohistochemically detected in large granular cells on the morning of the pro-oestrus day. These results indicate that GM-CSF may be involved in the regulation of ovarian histamine secretion in mast cells partially by enhancing interleukin-1beta-induced histamine release in the process of ovulation.

Animals↗

PubMed1999

Evidence for gonadotropin-releasing hormone receptor mRNA expression by estrogen in rat granulosa cells.

The hormonal regulation of ovarian gonadotropin-releasing hormone (GnRH) receptor mRNA expression has been examined by in situ hybridization in hypophysectomized immature rats. In hypophysectomized rats, GnRH receptor mRNA expression is localized in the interstitial cells. After diethylstilbestrol treatment, most follicles grow to form early antral follicles and express GnRH receptor mRNA in the peripheral part of the granulosa layer, indicating that the expression in the growing follicles is estrogen-dependent. Only weak or no expression of the receptor mRNA is detectable in the atretic follicles of hypophysectomized rats, whereas very strong expression has been observed in the granulosa cells of atretic follicles of intact immature rats. Administration of testosterone or a GnRH agonist, both of which are atretic agents for ovarian follicles, to hypophysectomized rats markedly increases the apoptotic cell death of the granulosa cells but fails to induce GnRH receptor mRNA expression. The co-administration of these agents with diethylstilbestrol causes the granulosa cells of atretic follicles to express the receptor mRNA very strongly, suggesting that this mRNA expression in the atretic follicles is also estrogen-dependent. On the other hand, expression of the receptor mRNA in the ovarian interstitial cells is not affected by hypophysectomy or hormone treatments. All of these results clearly indicate that estrogen is essential for the expression of ovarian GnRH receptor mRNA in the granulosa cells of atretic follicles and growing follicles, whereas the expression in the interstitial cells is estrogen-independent.

Animals↗

PubMed1999

Identification of podocalyxin-like protein 1 as a novel cell surface marker for hemangioblasts in the murine aorta-gonad-mesonephros region.

Recent studies with avian embryos and murine embryonic stem cells have suggested that hematopoietic cells are derived from hemangioblasts, the common precursors of hematopoietic and endothelial cells. We molecularly cloned podocalyxin-like protein 1 (PCLP1) as a novel surface marker for endothelial-like cells in the aorta-gonad-mesonephros (AGM) region of mouse embryos, where long-term repopulating hematopoietic stem cells (LTR-HSCs) are known to arise. PCLP1+ CD45 cells in the AGM region incorporated acetylated low-density lipoprotein and produced both hematopoietic and endothelial cells when cocultured with OP9 stromal cells. Moreover, multiple lineages of hematopoietic cells were generated in vivo when PCLP1 +CD45-cells were injected into neonatal liver of busulfan-treated mice. Thus, PCLP1 can be used to separate hemangioblasts that give rise to LTR-HSCs.

Amino Acid Sequence↗

PubMed1999

Gonadotropin-releasing hormone receptor mRNA expression in the ovaries of neonatal and adult rats.

Recent studies have shown that gonadotropin-releasing hormone (GnRH) can exert various effects on the rat ovary by acting through its specific receptors. To determine the cell types responsive to the action of GnRH under physiological conditions in the ovary, distribution of the GnRH receptor mRNA was studied histologically by in situ hybridization in neonatal and adult rats. Expression of the luteinizing hormone receptor mRNA was also examined to judge the growing state of follicles and the corpora lutea. In neonatal rat ovaries, no significant GnRH receptor mRNA signal was detected until 5 days after birth. The expression was first observed at 10 days in the interstitial cells. At 15 days of age, the receptor mRNA was expressed in the granulosa cells of most preantral and early antral follicles, while no hybridization signal was detected in oocyte and theca cells. In adult cycling rats, GnRH receptor mRNA was detected mainly in the granulosa cells of most follicles and luteal cells. The granulosa cells of atretic follicles showed a very high level of the mRNA expression throughout their degenerating process. A strong hybridization signal was also detected in the mural granulosa cells of mature follicles. Newly formed (developing) corpora lutea exhibited signals with moderate intensity in the luteal cells, and the older ones showed weaker signals. The finding that the initial expression of GnRH receptor mRNA was seen in the interstitial cells of neonatal ovaries implies an unknown function of the ovarian GnRH receptor in ovarian development. The high level expression of GnRH receptor mRNA in atretic and mature follicles supports the putative roles of GnRH in the induction of follicular atresia and ovulation in rat ovaries.

Animals↗

PubMed1999

Different mechanisms for testosterone-induced relaxation of aorta between normotensive and spontaneously hypertensive rats.

The tension in isolated ring preparations of the thoracic aortae from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) was measured isometrically to study the differences in testosterone-induced relaxation between WKY and SHR aortic rings. Testosterone (9 to 300 micromol/L) induced a concentration-dependent relaxation in both WKY and SHR aortic rings, and the relaxation induced by testosterone was greater in SHR than WKY. The relaxation induced by testosterone was significantly reduced by denudation of endothelium in SHR but not WKY. Indomethacin, an inhibitor of cyclooxygenase, and N(G)-nitro-L-arginine, an inhibitor of nitric oxide (NO) synthase, showed little influence on the relaxation induced by testosterone in both WKY and SHR aortic rings. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, significantly reduced the relaxation induced by testosterone in both WKY and SHR aortic rings, although the extent of reduction was greater in WKY than SHR. On the other hand, 4-aminopyridine, a selective inhibitor of voltage-dependent potassium channels, and tetraethylammonium, an inhibitor of calcium-activated potassium channels, significantly reduced the relaxation induced by testosterone in SHR but not WKY. These results suggest that the mechanisms of testosterone-induced vasorelaxation in both WKY and SHR involve, in part, ATP-sensitive potassium channels in the thoracic aortae and that in SHR aortic rings, testosterone may release endothelium-derived substances that may cause hyperpolarization of the cells by a mechanism that involves potassium channels. Moreover, the data show differences between WKY and SHR in the function of ATP-sensitive, voltage-dependent, and calcium-activated potassium channels.

4-Aminopyridine↗

PubMed1999

The expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its regulation by ovarian steroids in rat uterine stromal cells.

The effects of ovarian steroids on the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in rat uterus were examined. Intense expression of GM-CSF mRNA was dispersedly located in the endometrial-myometrial junction and stroma of the uterus. GM-CSF was immunohistochemically localized in stromal cells and luminal epithelium. Ovariectomy significantly reduced the appearance of GM-CSF-mRNA-positive cells and the levels of expression for GM-CSF mRNA in the whole uterus, whereas treatment with 17beta-estradiol (E2) or a combination of E2 and progesterone (P4) for 5 days on ovariectomized animals recruited GM-CSF-mRNA-positive cells and stimulated its expression. The combined treatment with E2 and P4 also stimulates the expression for GM-CSF mRNA and the production of immunoreactive GM-CSF in the stromal tissues. These data suggest that the expression of GM-CSF in uterine stromal cells is partially regulated by ovarian steroids.

Animals↗

PubMed1998

A variation in acetylcholine-induced relaxation of rat aorta in pregnancy.

The tension of isolated ring preparations of the thoracic aortae from pregnant rats on Days 7, 14, and 21 was measured isometrically to study the effect of advancing pregnant stage on endothelium-dependent relaxing factor activity. The endothelium-dependent relaxation caused by acetylcholine (ACh) (10(-8) - 3x10(-5) M) in the aortae of pregnant rats on Days 7, 14, and 21 were greater than that in those of diestrus (D-2) rats. In pregnant rats, the endothelium-dependent relaxation caused by acetylcholine was greatest in the aortae from pregnant rats on Day 21. In contrast with ACh, the relaxation caused by sodium nitroprusside was decreased in the aortae from pregnant rats on Day 21, compared with metestrus (D-1) and estrus (E) rats. The peaks of serum estradiol and progesterone levels in pregnant rats were observed on Days 21 and 14, respectively. These results suggest that there is a fluctuation of endothelium-dependent relaxing factor activity in the aortae during pregnancy of rats and ACh-induced relaxation is greatest on Day 21 in pregnancy, and that it may be due to the enhancement of NO synthesis in endothelium mainly by estradiol and partly by progesterone.

Acetylcholine↗

PubMed1998

Distinct roles of oncostatin M and leukemia inhibitory factor in the development of primordial germ cells and sertoli cells in mice.

Leukemia inhibitory factor (LIF) stimulates the growth of primordial germ cells (PGCs) in mouse embryo. However, as neither mice lacking LIF nor mice lacking the LIF receptor show defects in PGC growth, an alternate cytokine for PGC growth has been postulated. We investigated the role of mouse oncostatin M (mOSM), which is structurally and functionally related to LIF, in germ cell development. While LIF enhanced the survival of migratory as well as postmigratory PGCs, mOSM acted only on the postmigratory PGCs. Consistent with its biological activity, mOSM was found to be expressed in developing gonads. In the male, Sertoli cells in neonatal testis express mOSM; however, its expression is downregulated in adult testes. Moreover, mOSM enhanced the proliferation of Sertoli cells derived from neonatal testes in vitro more than human OSM or LIF. In contrast, postnatal ovaries do not express mOSM. These results indicate that mOSM is a stage- and sex-specific autocrine growth factor for Sertoli cells.

Animals↗

PubMed1998

Ovarian immune cells express granulocyte-macrophage colony-stimulating factor (GM-CSF) during follicular growth and luteinization in gonadotropin-primed immature rodents.

To obtain clues as to whether granulocyte-macrophage colony-stimulating factor (GM-CSF) is related to ovarian physiology, the sites, the gene expression and the production of GM-CSF in the ovary during follicular development and luteinization were studied in equine CG (eCG)-primed immature mice and rats. During follicular development, the expression of GM-CSF mRNA was localized in theca-interstitial tissues, oocytes and granulosa cells of small developing follicles in mice. In the mouse ovary after ovulation, luteal tissues as well as the above components had intense signals for GM-CSF mRNA. Mast cells, which were present mainly in the ovarian medulla, also expressed mRNA for GM-CSF in rats. Immunohistochemical analyses with two different antibodies against murine GM-CSF revealed that GM-CSF-like immunoreactivity was detectable mainly in theca-interstitial, luteal tissues, oocytes and mast cells. Intense GM-CSF positive cells in theca-interstitial and luteal tissues were stained with anti-CD11b antibody in mice. Messenger RNAs for GM-CSF receptor subunits were expressed in mast cells of the medulla and in luteal tissues in rat ovary. The levels of GM-CSF released into the culture media by rat ovarian dispersed cells 1-2 days after eCG treatment were higher than those before the treatment, although no significant change in the levels of ovarian GM-CSF mRNA was detected by reverse transcription-polymerase chain reaction analysis. The secretion of GM-CSF was also increased by treatment of the cells with immune stimulators such as phorbol ester, interleukin-1 and lipopolysaccharide. These data indicate that ovarian macrophages and mast cells in addition to theca-interstitial cells, synthesize and release GM-CSF during ovarian cycles, and that ovarian GM-CSF secreting capacity is enhanced during early stages of follicular development in rodents.

Animals↗

PubMed1998

Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich cell edges.

Stimulation of endothelial cells (ECs) with ATP evoked an increase in intracellular Ca2+ concentration ([Ca2+]i). In a single bovine aortic EC, the [Ca2+]i rise started at a specific peripheral locus and propagated throughout the entire cell as a Ca2+ wave. The initiation locus was constant upon repeated stimulation with ATP or other agonists (bradykinin and thrombin). The Ca2+ wave was unaffected by the removal of extracellular Ca2+, demonstrating its dependence on intracellular Ca2+ release. Microinjection of heparin into the cell inhibited the ATP-induced Ca2+ responses, indicating that the Ca2+ wave is at least partly mediated by the inositol 1,4, 5-trisphosphate receptor. Immunofluorescence staining revealed that caveolin, a marker protein for caveolae, is distributed heterogeneously in the cell and that Ca2+ waves preferentially originate at caveolin-rich cell edges. In contrast to caveolin, internalized transferrin and subunits of the clathrin-associated adaptor complexes such as adaptor protein-1 and -2 were diffusely distributed. Disruption of microtubules by Colcemid led to redistribution of caveolin away from the edges into the perinuclear center of the cell, and the ATP-induced [Ca2+]i increase was initiated on the rim of the centralized caveolin. Thus, caveolae may be involved in the initiation of ATP-induced Ca2+ waves in ECs.

Adaptor Protein Complex alpha Subunits↗

PubMed1998

Inhibitory regulation of inhibin gene expression by thyroid hormone during ovarian development in immature rats.

To explore the role of the thyroid gland in ovarian development during the initiation process of puberty, we examined the effects of hypothyroidism on the secretion of ovarian hormones during equine chorionic gonadotropin (eCG)-induced follicle development in immature female rats. Immature rats at 22 days of age were thyroidectomized (Tx) to cause hypothyroidism and then given a single s.c. injection of 5 IU eCG at 26 days of age to induce normal first ovulation. The blood samples were collected at 0, 24, and 48 h after eCG treatment to measure inhibin and estradiol by radioimmunoassay. Serum inhibin and estradiol levels in eCG-primed Tx animals were significantly higher at 24 and 48 h after eCG treatment than those in controls (eCG treated non-Tx rats). The number of healthy follicles larger than 400 microns in diameter and ovarian weight were significantly increased in Tx rats at 48 h after eCG treatment, compared to those in controls. The number of oocytes which are ovulated by an injection of human chorionic gonadotropin (10 IU) was significantly increased on the day after eCG treatment, compared to that of eCG treated non-Tx rats. The increments in both hormones levels, the number of large antral follicles, and ovarian weight in eCG-primed Tx animals were suppressed up to control levels with daily administrations of 5.0 micrograms thyroxine (T4) for 6 days during 22 to 27 days of age. The expression of mRNAs for inhibin alpha and beta A subunits increased in eCG-primed Tx rats at 48 hr after eCG treatment, and the increase in inhibin mRNAs was suppressed by T4 treatment up to control levels. These results clearly demonstrate that thyroid hormone takes part in an inhibitory regulation of ovarian hormonal secretion and folliculogenesis in eCG-primed immature female rats.

Animals↗

PubMed1998

In vitro expansion of murine multipotential hematopoietic progenitors from the embryonic aorta-gonad-mesonephros region.

The origin of hematopoietic stem cells (HSCs) and their growth factor requirement are poorly understood. Here we describe a new in vitro culture system of the aorta-gonad-mesonephros (AGM) region, where long-term repopulating HSCs first arise. We demonstrate that oncostatin M (OSM) is expressed in the AGM and is absolutely required for the expansion of multipotential hematopoietic progenitors in vitro. In addition, OSM enhances the formation of endothelial cell clusters. Thus, OSM appears to be a key cytokine for the development of multipotential hematopoietic progenitors in the AGM, possibly acting on common precursor cells between HSCs and endothelial cells. By using the AGM culture derived from macrophage colony-stimulating factor (M-CSF)-deficient op/op mutant embryos, we also show a pivotal role for M-CSF in fetal myelopoiesis.

Animals↗

PubMed1998

Caveolae: from a morphological point of view.

Caveolae in the plasma membrane have been a focus of intensive research during the past several years. There has been confusion concerning caveolae and caveola-like membrane domains, but it is now generally thought that the latter is a region distinct from caveolae. However, due to similar buoyancy of caveolae and caveola-like membranes, whether caveolae in situ are enriched with a given molecule is often difficult to be concluded by biochemical techniques alone. Furthermore, relatively shallow caveolae may be detected by some techniques, but not by others. Thus whether a molecule is enriched in caveolae should be confirmed by methods based on different principles. Among many putative caveolar molecules, those related to Ca2+ influx and extrusion were shown to be concentrated in caveolae by both immunocytochemical and biochemical techniques. In conjunction with other characteristics, the result implies that caveolae may function as a mobile compartment for Ca2+ signalling.

Animals↗

PubMed1998

Blockage of gonadotropin-induced first ovulation caused by thyroidectomy and its possible mechanisms in rats.

To determine the role of the thyroid gland on the ovarian functions during the initiation process of puberty, we examined the effects and its mechanisms of hypothyroidism on the first ovulation induced by equine chorionic gonadotropin (eCG) in immature female rats. Animals were thyroidectomized on day 22 and were injected with 5 IU of eCG on day 26 to induce the first ovulation on day 29. The number of antral follicles that secrete inhibin and the ovarian weight were significantly increased in thyroidectomized rats (Tx rats) 48 h after eCG treatment compared with those in non-Tx rats. However, thyroidectomy (Tx) significantly suppressed the rates of ovulating animals on day 29. The blockage of ovulation in Tx rats was recovered by administration of human chorionic gonadotropin or luteinizing hormone (LH)-releasing hormone (LHRH) on day 28. Inhibition of serum LH (not follicle-stimulating hormone) levels induced by Tx was almost restored to control levels by injection of LHRH. A significant increment in prolactin levels in Tx rats was also observed on day 28. The present data indicate that Tx before puberty in female rats causes the blockage of the first ovulation and that the inhibitory effects on ovulation are mainly due to the reduction in the preovulatory LH surge, which is partially mediated through an inhibition of LHRH action on the secretion of LH.

Animals↗