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2000 Fiscal Year Final Research Report Summary

Regulation of growth hormone secretagogue receptor gene expression

Research Project

Project/Area Number 11671101
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionNippon Medical School

Principal Investigator

KAMEGAI Jun  Nippon Medical School, Medicine, Assistant Professor, 医学部, 講師 (20204638)

Project Period (FY) 1999 – 2000
KeywordsGHS / GHS receptor / ghrelin
Research Abstract

Growth hormone secretagogues (GHSs) are synthetic peptide and nonpeptide compounds that stimulate the release of GH acting on the hypothalamus and pituitary. The GHS receptor (GHS-R) has been cloned, and the existence of the endogenous ligand has been assumed. Recently, an endogenous peptide ligand for the GHS receptor, ghrelin, was purified from the rat stomach and subsequently cloned by Kangawa et.al. However, the physiological significance of ghrelin is not clear. In this study, we found several new insights concerning GHS/GHS-R axis.
1. GHRH infusion resulted in a 2.5-fold increase in GHS-R mRNA levels of the rat pituitary. GHRH does not induce GHS-R mRNA levels of primary cell cultures from normal rat pituitaries in vitro, suggests that other systemic or central factors are necessary for GHRH-initiated augmentation of GHS-R synthesis.
2. GHS infusion reduced GHS-R mRNA levels significantly. This phenomenon was reproduced by adding GHS to the rat primary pituitary cell cultures, suggesting that the action of GHS on pituitary GHS-R mRNA levels is, at least in part, due to a direct interaction with the pituitary. These studies also indicate that GHS, like GHRH, can rapidly downregulate its own receptor message.
3. We examined the effect of glucocorticoids and thyroid hormones on pituitary GHS-R mRNA levels. We found that glucocorticoids directly increase pituitary GHS-R mRNA levels by stimulating GHS-R gene transcription, whereas T3 increases GHS-R mRNA levels in vitro by increasing message stability.
4. We found that central ghrelin administration increased hypothalamic Agouli-related protein (AGRP) mRNA levels as well as increased food intakes. On the other hand, 1μg of rat ghrelin central administration did not alter the episodic GH release of freely moving adult male rats. Thus ghrelin has an alternative role in stimulating food intake via an increase of AGRP than GH release from the pituitary.

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Kamegai J.: "Growth Hormone-releasing Hormone receptor (GHRH-R) and growth hormone secrefagogue receptor (GHS-R) mRNA levels during postnatal development in male and female rats,"J.Neuroendocrinol. 11. 299-306 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kineman R.D.: "Growth Hormone-releasing hormone (GHRH) and the growth hormone secrefagogue (GHS), L692, 585 differentially modulate rat pituitary GHS receptor (GHS-R) and GHRH receptor (GHRH-R) mRNA levels"Endocrinology. 140. 3581-3586 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugihara H.: "Effect of insulin-like growth factor-1 on growth hormone-releasing factor receptor expression in primary rat anterior pituitary cell cultures."Neurosci Lett.. 276. 87-90 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura H.: "Masculinizing effect of dihydrolastustere on growth hormone secretion is inhibited in ovariects rats with anterolateral deafferentation of the medial basal hypothalamus or in intact female rats"J.Neuroendocrinol. 12. 369-376 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura H.: "Glucocorticoids regulate pituitary growth hormone secretagogue receptor (GHS-R) gene expression."J.Neuroendocrinol. 12. 481-485 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Frohman L.A.: "Secretagogues and the somatotrope : signaling and proliferation."Recent Prog Horm Res. 55. 269-291 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Park S.: "Modulation of pituitary somatostatin receptor subtype (sst1-5) messenger ribonucleic acid levels by changes in the growth hormone axis."Enolocrinology. 141. 3556-3563 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kamegai J.: "Central effect of gheelin, an endogenous growth hormone secretagogue, on hypothalamic peptide gene expression."Endocrinology. 141. 4797-4800 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kamegai J: "Ereugen receptor (ER) α, but not ERβ gene is expressed in growth hormone releasing hormone neurons of the male rat hypothalamus"Endocrinology. 142. 538-543 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shuto Y.: "Generation of polyclonal antiserum against the growth hormone secretagoue recepor (GHS-R) : Evidence that the GHS-R exists in th hypothalamus, pituitary and stomal of rats."Life Sci. 68. 991-996 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kemegai J.: "Thyroid hormones regulate pituitary growth hormone secretagogue receptor (GHS-R) gene expression."J.Neuroendcrinol. 13. 275-278 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kamegai J, Wakabayashi I, Kineman RD, Frohman LA.: "Growth hormone-releasing hormone receptor (GHRH-R) and growth hormone secretagogue receptor (GHS-R) mRNA levels during postnatal development in male and female rats"J Neuroendocrinol. 11. 299-306 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kineman RD, Kamegai J, Frohman LA.: "Growth hormone-releasing hormone (GHRH) and the growth hormone secretagogue (GHS), L692,585, differentially modulate rat pituitary GHS receptor (GHS-R) and GHRH receptor (GHRH-R) mRNA levels"Endocrinology. 140. 3581-3586 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugihara H, Emoto N, Tamura H, Kamegai J, Shibasaki T, Minami S, Wakabayashi I: "Effect of insulin-like growth factor-1 on growth hormone-releasing factor receptor expression in primary rat anterior pituitary cell culture"Neurosci Lett. 276. 87-90 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura H, Sugihara H, Kamegai J , Minami S, Wakabayashi I.: "Masculinizing effect of dihydrotestosterone on growth hormone secretion is inhibited in ovariectomized rats with anterolateral deafferentation of the medial basal hypothalamus or in intact female rats."J Neuroendocrinol. 12. 369-376 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura H, Kamegai J, Sugihara H, Kineman RD, Frohman LA, Wakabayashi I: "Glucocorticoids regulate pituitary growth hormone secretagogue receptor (GHS-R) gene expression"J Neuroendocrinol. 12. 481-485 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Frohman LA, Kineman RD, Kamegai J, Park S, Teixeria LT, Coschigano KT, Kopchick JJ.: "Secretagoues and the somatotrope : signaling and proliferation."Recent Prog Horm Res. 55. 269-291 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Park S, Kamegai J, Johnson TA, Frohman LA, Kineman RD.: "Modulation of pituitary somatostatin receptor subtype (sst1-5) messenger ribonucleic acid levels by changes in the growth hormone axis"Endocrinology. 141. 3556-3563 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Wakabayashi I.: "Central effect of ghrelin, an endogenous growth hormone secretagogue, on hypothalamic peptide gene expression."Endocrinology. 141. 4797-4800 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Wakabayashi I.: "Estrogen receptor (ER)α, but not ERβ, gene is expressed in growth hormone releasing hormone neurons of the male rat hypothalamus."Endocrinology. 142. 538-543 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shuto Y, Shibasaki T, Wada K, Parhar I, Kamegai J, Sugihara H, Oikawa S, Wakabayashi I.: "Gneration of polyclonal antiserum against the growth hormone secretagogue receptor (GHS-R) ; Evidence that the GHS-R exists in the hypothalamus, pituitary and stomach of rats"Life Sci. 68. 991-996 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kamegai J, Tamura H, Ishii S, Sugihara H, Wakabayashi I.: "Thyroid hormones regulate pituitary growth hormone secretagogue receptor (GHS-R) gene expression."J Neuroendocrinol. 13. 275-278 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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