Search Results

You are looking at 1 - 9 of 9 items for

  • Author: M Noguchi x
  • Refine by Access: All content x
Clear All Modify Search
Restricted access

T. Noguchi, M. Kudo, T. Sugisaki, and I. Satoh


The hyt mutant mouse used in this study has a hypoplastic thyroid gland and is characterized by retarded somatic growth, very low to undetectable levels of plasma thyroxine (T4), and increased levels of plasma thyroid-stimulating hormone (TSH). This congenital hypothyroid mouse is therefore an ideal model for studying the effects of thyroid hypofunction on the adenohypophysis.

The anterior pituitary of the hyt mouse appeared less granular than that of the normal control when viewed by light microscopy, owing to a decrease in the population of somatotrophs. Many cells, in various stages of transformation into 'thyroidectomy cells', were recognized by the appearance of the characteristic granules and dilated rough endoplasmic reticulum. In some cases, the enlarged rough endoplasmic reticulum also contained spherical electron-dense secretory granules. In addition there were many cells undergoing mitosis and these were identified as thyrotrophs by their characteristic granules.

Administration of T4 during the first 40 days of life prevented the abnormal changes in the hyt anterior pituitary.

A reduction in immunoreactive thyrotrophin-releasing hormone (TRH) levels was seen in the median eminence of the hyt mouse. Treatment with T4 restored this to normal, suggesting that the reduced TRH content of the hypothalamus of the mutant mouse may be due to T4 deprivation.

J. Endocr. (1986) 109, 163–168

Free access

M Imae, Y Inoue, Z Fu, H Kato, and T Noguchi

Hepatocyte nuclear factor-3 (HNF-3) belongs to a large family of forkhead transcription factors and is made up of three members (HNF-3alpha, -3beta and -3gamma). It has been shown that HNF-3 regulates a number of metabolically important genes. However, the mechanisms underlying this regulation of HNF-3 activity by hormones and nutrition have not yet been well elucidated. In attempting to explore the regulation of gene expression of HNF-3 members by physiological status, we analyzed the effects of insulin, dexamethasone and protein malnutrition on the hepatic mRNA level of each member. Male Wistar rats were fed on a 12% casein diet, 12% gluten diet (deficient in lysine and threonine) or a protein-free diet for 1 week. The protein-free diet and gluten diet caused a 3. 7-fold increase in HNF-3g mRNA in the liver and did not affect the mRNA level of either HNF-3alpha or HNF-3beta. Daily administration of dexamethasone caused the mRNA levels of HNF-3alpha and HNF-3beta to increase (2.3- and 1.4-fold, respectively), but had no effect on the HNF-3gamma mRNA level. In diabetic rats that had been injected with streptozotocin, an elevation of the hepatic mRNA levels of HNF-3beta and HNF-3gamma was observed (1.6-and 1.9-fold, respectively). Insulin replacement in the diabetic rats decreased both mRNA levels in a dose-dependent manner. HNF-3alpha mRNA was not affected by insulin status. These results show that the genes of the three members of the HNF-3 family respond differently to hormonal and nutritional factors suggesting that the activities of HNF-3 members are regulated, at least in part, by the levels of their gene expression.

Restricted access

K Noguchi, J Arita, A Nagamoto, M Hosaka, and F Kimura


We investigated the effects of testosterone on FSH secretion from male rat anterior pituitary cells in culture at the single cell level. Anterior pituitary cells cultured with or without 10 ng/ml testosterone for 72 h were mono-dispersed and subjected to cell immunoblot assays for FSH. Cell blots specific for FSH were quantified by means of a microscopic image analyzer. The number of FSH-secreting cells detected as immunoreactive cell blots on the transfer membrane represented 4·1% of total pituitary cells applied on the membrane. The amount of FSH secreted by single cells varied from <20 to >8 000 fg/cell/h. The number of FSH-secreting cells was not changed by the addition of 10 ng/ml testosterone into the culture medium. Testosterone administration increased the mean FSH secretion by 64% after 3 h incubation, resulting in a shift to the right in the frequency distribution of FSH secretion from single cells. The total amount of FSH, namely the sum of FSH secreted by each FSH-secreting cell, was increased by 92% by the addition of testosterone. However, mean amounts of FSH secretion by the top ten cells of the largest secretor subgroup (>5 pg/cell/3 h) were not different between control and testosterone-treated groups.

The present study analyzed, for the first time, FSH secretion from rat anterior pituitary cells at the single cell level. The results suggest that stimulation by testosterone of FSH secretion in vitro is not due to an increase in the number of FSH-secreting cells but to an increase in FSH secretion from each cell.

Journal of Endocrinology (1996) 148, 427–433

Free access

M Noguchi, Y Ikarashi, M Yuzurihara, Y Kase, JT Chen, S Takeda, M Aburada, and A Ishige

The effects of a Japanese herbal medicine, Keishi-bukuryo-gan, and 17beta-estradiol on calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature were investigated in ovariectomized (OVX) rats. Ovariectomy not only potentiated CGRP-induced elevation of skin temperature and arterial vasorelaxation but also induced a lower concentration of endogenous CGRP in plasma and up-regulation of arterial CGRP receptors, suggesting that lowered CGRP in plasma due to ovarian hormone deficiency increases the number of CGRP receptors and consequently amplifies the stimulatory effects of CGRP to elevate skin temperature. Oral Keishi-bukuryo-gan (100-1000 mg/kg, once a day for 7 days) restored a series of CGRP-related responses observed in OVX rats by normalizing plasma CGRP levels in a dose-dependent manner as effectively as s.c. injection. 17Beta-estradiol (0.010 mg/kg, once a day for 7 days). However, Keishi-bukuryo-gan did not affect the lower concentration of plasma estradiol and the decreased uterine weight due to ovariectomy, although the hormone replacement of 17beta-estradiol restored them. These results suggest that Keishi-bukuryo-gan, which does not confer estrogen activity on plasma, may be useful for the treatment of hot flashes in patients for whom estrogen replacement therapy is contraindicated, as well as menopausal women.

Restricted access

K. Kizuki, A. Kitagawa, M. Takahashi, H. Moriya, M. Kudo, and T. Noguchi


The localization of tissue kallikrein in the pituitary gland of rats was investigated by an immunohistochemical technique using antiserum against rat urinary kallikrein. Kallikrein-positive cells were detected in the anterior lobe of the pituitary of both male and female rats, but were not observed in the posterior lobe of the pituitary in either sex.

The kallikrein-positive cells in the anterior pituitary of female rats in oestrus were found to correspond to the prolactin-producing cells, whereas the cells producing GH, LH and ACTH were negative for kallikrein. It is possible, therefore, that the tissue kallikrein may be involved in the production of prolactin and not that of the other anterior pituitary hormones, such as GH, LH, FSH, ACTH and TSH.

Journal of Endocrinology (1990) 127, 317–323

Free access

M Noguchi, Y Ikarashi, M Yuzurihara, K Mizoguchi, K Kurauchi, JT Chen, and A Ishige

We investigated the mechanism for the augmentation of the calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature in ovariectomized (OVX) rats. I.v. injection of alphaCGRP (10 micro g/kg) elevated skin temperature of the hind paws. The elevation was significantly greater in OVX rats than in sham-operated rats and was inhibited by pretreatment with human CGRP(8-37) (100-1000 micro g/kg i.v.), a CGRP receptor antagonist, in a dose-dependent manner. In addition, ovariectomy not only potentiated vasorelaxation due to alphaCGRP but increased the number of CGRP receptors in mesenteric arteries. Further, the plasma concentration of endogenous CGRP was significantly lower in OVX rats. These results suggest that the low concentration of plasma CGRP due to ovarian hormone deficiency may induce the increase in the number of CGRP receptors due to up-regulation. Therefore, the increased number of CGRP receptors may be responsible for potentiation of exogenous alphaCGRP-induced elevation of skin temperature in OVX rats. The mechanism underlying the hot flashes observed in menopausal women may also involve, in part, the up-regulation of CGRP receptors following ovarian hormone deficiency.

Restricted access

A Takenaka, M Mori, S Yamada, J Ohgane, S-I Takahashi, and T Noguchi


The plasma concentration and liver mRNA content of IGF-I are regulated by the quantity and quality of dietary proteins. To determine whether the synthesis of IGF-binding proteins (BPs) is also affected by protein nutrition, we assessed plasma concentration, tissue mRNA content and liver transcription rate of each BP after rats were fed either a 12% casein or a protein-free diet for 1 week. Protein deprivation reduced the plasma concentration of IGFBP-3 and IGFBP-4 and increased that of IGFBP-1 and IGFBP-2. The mRNA content in tissues and liver transcription rates of IGFBP-3 and IGFBP-4 did not change in response to protein deprivation although their plasma concentrations decreased. The increased plasma IGFBP-1 and IGFBP-2 concentrations were explained by the increased mRNA content and transcription rate of their genes in the liver. Although IGFBP-1 mRNA was increased by protein deprivation not only in liver but also in kidney, IGFBP-2 mRNA was increased only in liver and did not increase in any other tissue examined. In addition, the liver mRNA content of the acid-labile subunit, which can form a ternary complex with IGFs and IGFBP-3, was not affected by protein deprivation. These results show that tissue-specific synthesis of each BP is regulated in a distinct way in response to protein deprivation.

Journal of Endocrinology (1996) 150, 33–41

Restricted access

Y Ito, M Ariga, S-I Takahashi, A Takenaka, T Hidaka, and T Noguchi


The binding of insulin to its receptor rapidly induces intrinsic insulin receptor tyrosine kinase activity, resulting in tyrosine phosphorylation of various cytosolic substrates, such as insulin receptor substrate-1 (IRS-1) which, in turn, associates with a p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) followed by activation of this enzyme.

In the present study, we have examined these early steps of insulin signalling in rat liver in vivo after food ingestion. After fasting for 22 h, a 12% casein diet was available ad libitum throughout the 8-h experimental period. Plasma insulin concentrations increased within 45 min after feeding, reached a maximum at 1·5 h and gradually decreased until 8 h. Autophosphorylation of the insulin receptor β-subunit in liver was detected even during fasting and increased about 1·5-fold at 1·5 h after feeding. Basal tyrosine phosphorylation of IRS-1 was detectable during starvation, increased about twofold at 3 h after feeding and levels were maintained until 8 h. The content of the p85 subunit of PI 3-kinase associated with IRS-1 also increased after feeding in parallel with the changes in tyrosine phosphorylation of IRS-1.

Because tyrosine phosphorylation of the insulin receptor β-subunit and IRS-1 and the association of the p85 subunit of PI 3-kinase with IRS-1 in liver were closely correlated with the changes in the plasma concentration of insulin, we concluded that endogenous insulin secreted in response to eating caused these insulin-dependent intracellular changes in the liver.

Journal of Endocrinology (1997) 154, 267–273

Free access

J Nagamine, R Nagata, H Seki, N Nomura-Akimaru, Y Ueki, K Kumagai, M Taiji, and H Noguchi

SM-130686, an oxindole derivative, is a novel orally active GH secretagogue (GHS) which is structurally distinct from previously reported GHSs such as MK-677, NN703 and hexarelin. SM-130686 stimulates GH release from cultured rat pituitary cells in a dose-dependent manner. Half-maximum stimulation was observed at a concentration of 6.3+/-3.4 nM. SM-130686-induced GH release was inhibited by a GHS antagonist, but not by a GH-releasing hormone antagonist. SM-130686 dose-dependently inhibited the binding of radiolabeled ligand, (35)S-MK-677, to human GHS receptor 1a (IC(50)=1.2 nM). This indicates that SM-130686 stimulates GH release through the GHS receptor. The effect of a single oral administration of SM-130686 on GH release in pentobarbital-anesthetized rats was studied. After treatment with 10 mg/kg SM-130686, plasma GH concentrations measured by radioimmunoassay significantly increased, reaching a peak at 20-45 min, and remained above baseline during the experimental period (60 min). The anabolic effect of repetitive SM-130686 administration was studied in rats. Rats received 10 mg/kg SM-130686 orally twice a day and were weighed every day for 9 days. At day 9 there was a significant increase in both the body weight and the fat free mass (19.5+/-2.1 and 18.1+/-7.5 g respectively). Serum IGF-I concentration was also significantly elevated 6 h after the last dose of SM-130686. An endogenous GHS ligand for the GHS receptor has recently been identified from stomach extract and designated as ghrelin. The GH-releasing activity in vitro relative to ghrelin (100%) was about 52% for SM-130686. It is likely that SM-130686 is a partial agonist for the GHS receptor. In summary, we describe here an orally active GHS, SM-130686, which acts through the GHS receptor. Repetitive administration of SM-130686 to rats, similar to repetitive administration of GH, significantly increased the fat free mass by an amount almost equal to the gain in body weight.