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Biomedical subjects

Hirokazu Matsumoto

Publications and source records attributed to Hirokazu Matsumoto.

At least 19 recordsLinked to original sources

Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats.

Metastin/kisspeptin, the KiSS-1 gene product, has been identified as an endogenous ligand of GPR54 that reportedly regulates GnRH/LH surges and estrous cyclicity in female rats. The aim of the present study was to determine if metastin/kisspeptin neurons are a target of estrogen positive feedback to induce GnRH/LH surges. We demonstrated that preoptic area (POA) infusion of the anti-rat metastin/kisspeptin monoclonal antibody blocked the estrogen-induced LH surge, indicating that endogenous metastin/kisspeptin released around the POA mediates the estrogen positive feedback effect on GnRH/LH release. Metastin/kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) may be responsible for mediating the feedback effect because the percentage of c-Fos-expressing KiSS-1 mRNA-positive cells to total KiSS-1 mRNA-positive cells was significantly higher in the afternoon than in the morning in the anteroventral periventricular nucleus (AVPV) of high estradiol (E(2))-treated females. The percentage of c-Fos-expressing metastin/kisspeptin neurons was not different between the afternoon and morning in the arcuate nucleus (ARC). Most of the KiSS-1 mRNA expressing cells contain ERalpha immunoreactivity in the AVPV and ARC. In addition, AVPV KiSS-1 mRNA expressions were highest in the proestrous afternoon and lowest in the diestrus 1 in females and were increased by estrogen treatment in ovariectomized animals. On the other hand, the ARC KiSS-1 mRNA expressions were highest at diestrus 2 and lowest at proestrous afternoon and were increased by ovariectomy and decreased by high estrogen treatment. Males lacking the surge mode of GnRH/LH release showed no obvious cluster of metastin/kisspeptin-immunoreactive neurons in the AVPV when compared with high E(2)-treated females, which showed a much greater density of these neurons. Taken together, the present study demonstrates that the AVPV metastin/kisspeptin neurons are a target of estrogen positive feedback to induce GnRH/LH surges in female rats.

Animals↗

Measurement of group refractive index wavelength dependence using a low-coherence tandem interferometer.

A technique for the measurement of the group refractive index wavelength dependence of optical materials using a low-coherence tandem interferometer and a spectrometer is proposed. Four channeled spectra resulting from interferences of light beams from different pairs of optical paths are used for the calculation of optical path differences. The group refractive index wavelength dependence is calculated from these optical path differences generated from the sample under measurement. No a priori information of the geometric thickness of a sample is required. The wavelength dependence of the group refractive index of the samples BK7 parallel plate of 5.200 and 10.025 mm from 675 to 850 nm is experimentally measured with an accuracy of the order of 10(-5) and a repeatability of the order of 10(-9).

Journal Article↗

Doppler-free spectroscopy using a continuous-wave optical frequency synthesizer.

A continuous-wave (cw) optical frequency synthesizer is demonstrated by using a monolithic-type cw optical parametric oscillator (cw-OPO) and an optical frequency comb. The cw-OPO is phase locked to an optical frequency comb that is phase locked to an atomic clock. The output frequency of the cw-OPO is frequency shifted with an electro-optic modulator, which makes it possible to tune the frequency continuously over 10 GHz. Furthermore, Doppler-free spectroscopy is performed using the optical frequency synthesizer for a cesium D1 line at 895 nm. The observed linewidth of 5 MHz is the natural linewidth of cesium. The center frequency of the line is consistent with a previous report.

Journal Article↗

Design, synthesis, and structure-activity relationships of thieno[2,3-b]pyridin-4-one derivatives as a novel class of potent, orally active, non-peptide luteinizing hormone-releasing hormone receptor antagonists.

Design, synthesis, and structure-activity relationships of thieno[2,3-b]pyridin-4-one-based non-peptide luteinizing hormone-releasing hormone (LHRH) receptor antagonists are described. Starting with the thienopyridin-4-one derivative 26d (T-98475) an optimization study was performed, which resulted in the identification of a highly potent and orally bioavailable LHRH receptor antagonist, 3-(N-benzyl-N-methylaminomethyl)-7-(2,6-difluorobenzyl)-4,7-dihydro-2-[4-(1-hydroxy-1-cyclopropanecarboxamido)phenyl]-5-isobutyryl-4-oxothieno[2,3-b]pyridine (33c). Compound 33c displayed subnanomolar in vitro activities for the human receptor and its oral administration caused effective suppression of the plasma LH levels in castrated male cynomolgus monkeys. Furthermore, SAR studies revealed that a hydroxyalkylamido moiety on the 2-phenyl ring is virtually equivalent to an alkylureido moiety, at least in this series of compounds.

Administration, Oral↗

Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats.

Ovulation is caused by a sequence of neuroendocrine events: GnRH and LH surges that are induced by positive feedback action of estrogen secreted by the mature ovarian follicles. The central mechanism of positive feedback action of estrogen on GnRH/LH secretion, however, is not fully understood yet. The present study examined whether metastin, the product of metastasis suppressor gene KiSS-1, is a central neuropeptide regulating GnRH/LH surge and then estrous cyclicity in the female rat. Metastin had a profound stimulation on LH secretion by acting on the preoptic area (POA), where most GnRH neurons projecting to the median eminence are located, because injection of metastin into the third ventricle or POA increased plasma LH concentrations in estrogen-primed ovariectomized rats. Metastin neurons were immunohistochemically found in the arcuate nucleus (ARC) to be colocalized with estrogen receptors with some fibers in the preoptic area (POA) in close apposition with GnRH neuronal cell bodies or fibers. Quantitative RT-PCR has revealed that KiSS-1 and GPR54 mRNAs were expressed in the ARC and POA, respectively. The blockade of local metastin action in the POA with a specific monoclonal antibody to rat metastin completely abolished proestrous LH surge and inhibited estrous cyclicity. Metastin-immunoreactive cell bodies in the ARC showed a marked increase and c-Fos expression in the early proestrus afternoon compared with the day of diestrus. Thus, metastin released in the POA is involved in inducing the preovulatory LH surge and regulating estrous cyclicity.

Animals↗

Electron microscopy examination of galanin-like peptide (GALP)-containing neurons in the rat hypothalamus.

Galanin-like peptide (GALP) is a novel peptide which is isolated from the porcine hypothalamus. GALP-containing neurons are present in the arcuate nucleus (ARC), being particularly densely concentrated in medial posterior regions. To observe the ultrastructure and synaptic relationships of GALP-containing neurons in the ARC, light and immunoelectron microscopy techniques were used. At the light microscope level, GALP-containing neurons were observed distributed rostrocaudally throughout the ARC, with the majority present in the posterior, periventricular zones. At the electron microscope level, many immunopositive dense-cored vesicles were evident in the perikarya, dendrites and axon terminals of the GALP-containing neurons. Furthermore, these neurons received synapses from immunonegative axon terminals that were symmetric in the case of synapses made on perikarya, and both asymmetric and symmetric for synapses made on dendrites. Axon terminals of GALP-containing neurons often made synapses on immunonegative dendrites. Such synapses were all symmetric. Synapses were also found between axon terminals and perikarya as well as dendrites of GALP-containing neurons. These findings suggest that the physiological role of the GALP-containing neurons in the ARC is based on complex synaptic relationships between GALP-containing neurons and either GALP-immunopositive or -immunonegative neurons.

Animals↗

Identification of the prolactin-releasing peptide-producing cell in the rat adrenal gland.

Prolactin-releasing peptide (PrRP) is a novel peptide found in bovine hypothalamus as an endogenous ligand of an orphan G-protein-coupled receptor (hGR3). It is known that PrRP is widely distributed and plays roles in the central nervous system (CNS). In particular, PrRP acts as a neurotransmitter that mediates stress and activates the hypothalamo-pituitary-adrenal axis. On the other hand, only a few studies have so far been performed on PrRP in peripheral tissues. Among peripheral tissues, appreciable levels of PrRP are found only in the adrenal gland; however, the PrRP-producing cells in the adrenal gland have not been identified. In this study, we detected PrRP mRNA in the rat adrenal medulla. So, we tried to identify the PrRP-producing cells in primary culture cells of the adrenal medulla. We found immunopositive PrRP cells among the cultured cells from the adrenal gland, but not in the adrenal gland tissue, by means of immunocytochemistry. The PrRP immunopositive cells were double positive for tyrosine hydroxylase (TH) and for phenylethanolamine N-methyltransferase (PNMT), which indicates that PrRP may be produced in a part of the adrenaline cells in the adrenal gland. This is the first report that PrRP is produced in the adrenaline-containing cells of the adrenal gland.

Adrenal Medulla↗

Neuronal interactions between galanin-like-peptide- and orexin- or melanin-concentrating hormone-containing neurons.

Galanin-like peptide (GALP) is a novel orexigenic neuropeptide that is recently isolated from the porcine hypothalamus. GALP-containing neurons predominantly locate in the hypothalamic arcuate nucleus (ARC). The expression of GALP mRNA within the ARC is increased after the administration of leptin. GALP-containing neurons express leptin receptor and contain alpha-melanocyte-stimulating hormone. We have recently reported that neuropeptide Y (NPY)- and orexin-containing axon terminals are in close apposition with GALP-containing neurons in the ARC. In addition, GALP-containing neurons express orexin-1 receptor (OX1-R). Thus, GALP may function under the influence of leptin and orexin. However, the target neurons of GALP have not yet been clarified. To clarify the neuronal interaction between GALP-containing and other feeding regulating neurons, double-immunostaining method using antibodies against GALP- and orexin- or melanin-concentrating hormone (MCH) was performed in the rat lateral hypothalamus (LH). GALP-immunoreactive fibers appeared to project to the LH around the fornix. They were also found from the rostral to the caudal part of the ARC, paraventricular nucleus (PVH), stria terminalis (BST), medial preoptic area (MPA), and lateral septal nucleus (LSV). Moreover, GALP-like immunoreactive nerve fibers were directly contacted with orexin- and melanin-concentrating hormone (MCH)-like immunoreactive neurons in the LH. Our findings strongly suggest that GALP-containing neurons interact with orexin- and/or MCH-containing neurons in the lateral hypothalamus and that it participates in the regulation of feeding behavior in harmony with other feeding-regulating neurons in the hypothalamus.

Animals↗

Estrogen suppresses the stress response of prolactin-releasing peptide-producing cells.

Prolactin-releasing peptide (PrRP) is known to be produced in A1/A2 noradrenergic neurons and to mediate the stress response. Our preliminary experiment showed that PrRP neurons in the A2 region differed between males and females in terms of c-Fos expression. In addition it has been reported that estrogen receptor alpha is detectable in A2 PrRP neurons. Therefore, we speculated that the stress response of PrRP neurons is modified by estrogen. We, therefore, examined c-Fos expression in A2 PrRP neurons during the estrous cycle and found that c-Fos accumulation in PrRP neurons was significantly decreased in estrus compared with in proestrus, metestrus and diestrus. This suggests that estrogen suppresses the activation of PrRP neurons. We thus administered diethylstilbestrol (DES) to ovariectomized rats and then added restraint stress. The data clearly showed that PrRP cells in DES-administered rats significantly suppressed c-Fos accumulation induced by stress.

Animals↗

Measurements and numerical analysis for femtosecond pulse deformations after propagation of hundreds of meters in air with water-vapor absorption lines.

We have clarified the influences of water-vapor absorption lines in air on femtosecond pulse propagations from experimental and theoretical points of view. Precise measurements for the femtosecond pulse shapes after propagation of as much as 300 m through air have been made in a semiunderground optical testing tunnel. We observed the pulse splitting and the enhancement of the pulse broadening due to the 100-m propagation in air. The experimental results are in good agreement with the theoretical analysis by use of the HITRAN database at the edge and the center of the water-vapor absorption regions in air. Measured autocorrelation traces are mostly reproduced by those calculated with only the real part (dispersion) of the refractive index modulated by water-vapor absorption lines in air. This fact enables us to conclude that the pulse deformations due to water absorption lines in air are caused mainly by the real part (dispersion), not by the imaginary part (absorption), of the refractive index of air.

Journal Article↗

Frequency stabilization of a 1319-nm Nd:YAG laser by saturation spectroscopy of molecular iodine.

Hyperfine transitions of molecular iodine were observed by use of the frequency-doubled output of a 1319-nm Nd:YAG laser with saturation spectroscopy. The laser frequency was stabilized to the observed hyperfine transition and reached a stability of 6 x 10(-12) for a 1.5-s averaging time, improving toward the 1 x 10(-12) level after 100 s. The iodine-stabilized 1319-nm Nd:YAG laser is an excellent candidate for an optical frequency standard for telecommunication applications.

Journal Article↗

Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat.

Metastin is a novel peptide that has been isolated from the human placenta as the cognate ligand of the G-protein-coupled receptor OT7T175 (or GPR54). However, its physiological functions have not yet been fully investigated. In the present study, we show that subcutaneous administration of metastin increased the plasma levels of gonadotropins (follicle-stimulating hormone and luteinizing hormone) and induced ovulation in prepubertal female rats that had been pretreated with pregnant mare serum gonadotropin to induce follicle maturation. Furthermore, metastin administration drastically increased the plasma levels of gonadotropins in male rats. This action was abolished by pretreatment with a GnRH antagonist, and was accompanied by induction of c-Fos immunoreactivity in GnRH neurons. These results suggest that s.c. administered metastin induces the release of gonadotropin via activation of the hypothalamic GnRH neurons.

Animals↗

Absolute frequency measurement of an acetylene-stabilized laser at 1542 nm.

The absolute frequency of an acetylene-stabilized laser at 1542 nm is measured at its second harmonic (771 nm) by use of a femtosecond optical comb based on a mode-locked Ti:sapphire laser. Frequency stability and reproducibility of the acetylene-stabilized laser are evaluated by the femtosecond comb with a H maser as a frequency reference. The absolute frequency of a laser diode stabilized on the P(16) transition of 13C2H2 is determined to be 194 369 569 383.6(1.3) kHz. The acetylene-stabilized laser serves as an important optical frequency standard for telecommunication applications.

Journal Article↗

Low-coherence tandem interferometer for measurement of group refractive index without knowledge of the thickness of the test sample.

A new low-coherence interferometric technique is proposed for measuring the group refractive indices of dispersive samples with high accuracy. A tandem configuration of interferometers is used to compensate for the asymmetrical distortion of interferograms that results from the broad spectrum of the light source. The group refractive index can be measured without knowledge of the geometrical thickness of the sample under test. The proposed technique can successfully measure even a thick sample. Computer calculations have shown the effectiveness of the proposed technique, which was verified by preliminary experiments; the difference between the experimental result and the catalog data was 7 x 10(-4).

Journal Article↗

Broad-spectrum frequency comb generation and carrier-envelope offset frequency measurement by second-harmonic generation of a mode-locked fiber laser.

A frequency comb spanning more than one octave has been achieved by injecting the second-harmonic generation (780 nm) of a mode-locked fiber laser (1.56 microm) into a photonic crystal fiber. We propose and realize a novel interferometric scheme for observing the carrier-envelope offset frequency of the frequency comb. Frequency noise has been observed on the measured carrier-envelope offset frequency, which has been confirmed to be generated in the photonic crystal fiber by comparing the measured beat frequencies between cw lasers and frequency combs before and after the photonic crystal fiber. The mode-locked fiber laser is considered to be an important candidate for the light source used in realizing a compact optical frequency measurement system including applications in the telecommunication bands.

Journal Article↗

Galanin-like peptide is target for regulation by orexin in the rat hypothalamus.

Galanin-like peptide (GALP) is a newly discovered 60 amino acid peptide from the porcine hypothalamus. GALP has been shown to be expressed predominantly in the arcuate nucleus (ARC) of the rat hypothalamus, a region considered to be one of the most important feeding-regulating centers in the brain. GALP-containing neurons in the ARC express leptin receptors, but relationships between GALP and other feeding-regulating neurons have not yet been fully elucidated. Given that Orexin (OX)-containing neurons make synaptic inputs to the ARC, we thus examined the relationship between GALP and OX in the ARC by use of a dual immunostaining technique. OX-immunoreactive fibers appeared to be closely apposed to GALP-immunoreactive cell bodies and their processes. We also examined whether the OX receptor, OX(1)-R was expressed in the GALP-containing neurons. Immunoreactivity for both OX(1)-R and GALP was detectable in 9.6 % neurons (range 4.2-14.6%) in the ARC. These findings strongly suggest that GALP may participate in the regulation of feeding behavior under the influence of leptin and OX.

Animals↗

Appearance of prolactin-releasing peptide-producing neurons in the area postrema of adrenalectomized rats.

Prolactin-releasing peptide (PrRP) was found to be a novel hypothalamic peptide that stimulates prolactin release in vitro and in vivo. In the normal adult rat brain, PrRP neurons are known to be located in only three areas, i.e. the dorsomedial hypothalamic nucleus, ventrolateral reticular formation; and nucleus of the tractus solitarius in the medulla oblongata. These PrRP neurons project neurites into various brain areas, including regions such as the paraventricular nucleus, supraoptic nucleus, and bed nucleus of the stria terminalis. Both PrRP nerve fibers and a high level of PrRP receptor, UHR-1, mRNA are observed in the area postrema (AP),but no PrRP neurons are detected in the AP of normal rats. In this study, we clearly demonstrated that PrRP-producing cells newly appeared in the AP of adrenalectomized rats by in situ hybridization and immunocytochemistry. Our results suggest that PrRP may have some important roles in the AP of adrenalectomized rats. This is the first report demonstrating the appearance of PrRP-positive cells in the AP.

Adrenalectomy↗

Changes in hypothalamic expression levels of galanin-like peptide in rat and mouse models support that it is a leptin-target peptide.

Galanin-like peptide (GALP) is a novel peptide that has been isolated from the porcine hypothalamus. The expression of GALP mRNA is localized to the hypothalamic arcuate nucleus and is thought to be under the regulation of leptin. First, we confirmed by real-time PCR analysis that sc administration of leptin to Wistar rats under food-deprived conditions resulted in a 1.5-fold increase in hypothalamic GALP mRNA levels. Next, GALP mRNA levels were found to be reduced by 50% in 11-wk-old male Zucker obese rats compared with age-matched Zucker lean rats, whereas neuropeptide Y mRNA levels were increased by 55% and proopiomelanocortin mRNA levels were reduced by 53% in Zucker obese rats. Analysis using a two-site enzyme immunoassay revealed a lower level of hypothalamic GALP immunoreactivity in 11-wk-old Zucker obese rats (5.9 fmol/mg protein) than in age-matched Zucker lean rats (19.6 fmol/mg protein). Immunohistochemical studies demonstrated that Zucker obese rats (11 wk old) had a reduced number of GALP immunoreactivity-positive cells (29.4 cells/3 slices) in the arcuate nucleus compared with age-matched Zucker lean rats (115 cells/3 slices). Furthermore, Zucker obese rats showed increased sensitivity to intracerebroventricularly administered GALP compared with Zucker lean rats, in that a lower dose of GALP increased plasma LH levels in male Zucker obese rats, but not in male Zucker lean rats. In addition, a reduction in the level of hypothalamic GALP mRNA was found in db/db and ob/ob mice. The result supports the hypothesis that the hypothalamic GALP gene expression is controlled by leptin signals and suggests possible involvement of GALP in the reproductive abnormalities of the Zucker obese rat.

Animals↗