The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Ghrh  -  growth hormone releasing hormone

Rattus norvegicus

Synonyms: GHRH, GRF, Growth hormone-releasing factor, Growth hormone-releasing hormone, Somatoliberin
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Ghrh

  • Gene expression of hypothalamic somatostatin, growth hormone releasing factor, and their pituitary receptors in hypothyroidism [1].
  • With replacement rGH, weight gain was restored, GHRH content increased but not fully to control, and SS content did not change [2].
  • Since mucosal proliferation was considered to contribute to healing of chronic gastroduodenal ulcerations, we designed the study to determine the interaction of GRF and somatostatin on the healing rate of acetic acid-induced chronic gastric and duodenal ulcers and on the growth of gastroduodenal mucosa in rats [3].
  • On the other hand, SRIF (100 nM) significantly antagonized the effect of GHRH, which was completely reversed by pretreatment with pertussis toxin (50 ng/ml) [4].
  • Taken together, these data indicate that although MtT/S cells express the GHRH-R, GHRH cannot stimulate adenylate cyclase to increase GH transcription due to constitutive elevation of cAMP levels, by a means that may be similar to that in cases of acromegaly not caused by oncogenic gsp mutations [5].

Psychiatry related information on Ghrh


High impact information on Ghrh


Chemical compound and disease context of Ghrh

  • Percent weight gain, GHRH content, and SS content in control adolescent (8 weeks) and adult rats (6 months) were compared in normal rats administered supraphysiologic amounts of rat growth hormone (rGH) or in hypophysectomized rats receiving thyroxine and corticosterone with or without physiologic rGH replacement [2].
  • To examine thyroid hormone regulation of the pituitary receptor for hypothalamic growth hormone (GH)-releasing factor (GRF), we studied effects of hypothyroidism on the pituitary GRF receptor (GRF-R) mRNA and its related parameters in rats [14].
  • Protein kinase C enhances growth hormone releasing factor (1-40)-stimulated cyclic AMP levels in anterior pituitary. Actions of somatostatin and pertussis toxin [15].
  • Male MSG-treated rats had lower body weight (-25%) and reduced hypothalamic GHRH (-89%) and pituitary GH content (-69%) compared to male controls [16].
  • In addition to increasing dopa synthesis in intact tissue, incubation of ganglia with rat growth hormone-releasing factor, secretin, vasoactive intestinal peptide or peptide histidine isoleucine amide also increased the activity of tyrosine hydroxylase measured subsequently in ganglion homogenates [17].

Biological context of Ghrh

  • Brief GHRH applications (30 nM, 40 s) triggered rhythmic action potentials (23.6 +/- 0.9 mV, 613 +/- 82 ms, 0.21 +/- 0.02 Hz) and [Ca2+]i increase (to 352 +/- 30 nM) followed by rhythmic [Ca2+]i transients (to 138 +/- 6 nM) that persisted up to 90 min after the last GHRH application [18].
  • Pretreatment with 1 microM SS for 48 h caused a shift in the IC50 of SS to inhibit 3-isobutyl-1-methylxanthine (IBMX) or growth hormone-releasing factor (GRF)-induced growth hormone (GH) and TRH + IBMX-induced thyroid-stimulating hormone (TSH) release by more than 2 orders of magnitude [19].
  • Up-regulation of hypothalamic GHRH-R by IL-1beta may explain previous findings suggesting that IL-1beta stimulates GHRH activity [20].
  • After treatment of the GH4 rat somatotroph cell line with rGHRH (10(7) M) for 2.5 min, there was robust phosphorylation of MAPK not seen in vehicle-treated cells [21].
  • GRF was not affected by 2DG or ISO in either genotypes [22].

Anatomical context of Ghrh

  • GH secretagogue (GHS)/ghrelin stimulates GH secretion by binding mainly to its receptor (GHS-R) on GHRH neurons in the arcuate nucleus (Arc) of the hypothalamus [23].
  • In this study, we demonstrated that ghrelin caused weaker GH secretion than that caused by GHRH, and we also showed that costimulation with GHRH had no additive or synergistic effect on GH secretion, suggesting that ghrelin indirectly affects coordinated GH release from pituitary gland, as found in vivo [24].
  • The difference in the regulation of GH and GH-releasing hormone (GHRH) receptor gene transcription in relation to the developmental stage of GH cells were examined in these two cell lines [25].
  • The aim of the present work was to study GRF regulation by these signals, using primary fetal rat hypothalamic-brain stem cell cocultures [26].
  • GRF injected subcutaneously twice daily at 100 micrograms/kg/day for 7 days resulted in a significant enhancement of healing rate of both gastric and duodenal ulcerations and this was accompanied by a significant increase in the weight of the mucosa and the contents of RNA and DNA [3].

Associations of Ghrh with chemical compounds

  • These data suggest that GRF and somatostatin regulate the mitotic activity of GH-producing cells and that the effect of GRF is possibly mediated by cyclic AMP [27].
  • KP-102 increased GHRH mRNA expression level in the presence of anti-NPY IgG [23].
  • 3. Somatostatin (1-300 nM), carbamylcholine (0.1-1 microM) and muscarine (0.1-1 microM) each had a dose-dependent inhibitory effect, from a decrease of Ca2+ spike duration and frequency to a complete block of the GHRH-evoked action potentials [18].
  • VIP is more active than rat GRF in stimulating adenylate cyclase activation [28].
  • The effect of SS on GRF in cocultures was examined by using a multiple approach: (1) depleting endogenous SS by adding 1 mM cysteamine (CSH); (2) blocking endogenous SS by incubation with SS antiserum, and (3) incubating with synthetic SS14 at different concentrations and exposure periods [26].

Physical interactions of Ghrh

  • Functional analysis of the two GHRH receptor isoforms demonstrates that both bind GHRH, but only the short isoform signals through a cAMP-mediated pathway [29].
  • To test this hypothesis, we have visualized radiolabeled SRIF-binding sites and GRF immunoreactivity (ir) in adjacent sections of the hypothalamus, by combined radioautography and immunohistochemistry [30].
  • Moreover, specific [125I] Tyr10-human GRF binding to pituitary cells was reduced significantly by IGF-I treatment [31].

Co-localisations of Ghrh

  • Galanin is a neuropeptide that is colocalized with GHRH in hypothalamic neurons and is thought to be involved in generating the episodic pattern of GH secretion [32].

Regulatory relationships of Ghrh

  • 4. The present results show that somatotrophs in culture have intrinsic membrane properties that allow them to sustain a pacemaker activity and subsequent long-lasting sequences of [Ca2+]i oscillations triggered by short pulses of GHRH and inhibited by somatostatin and muscarinic agonists [18].
  • It is also suggested that the reduction of GHRH neurons of Tg rats is induced by a decrease in GHS-R expression [23].
  • We performed dual chromogenic and autoradiographic in situ hybridization to determine whether GHRH neurons coexpress either the sst1 and/or sst2 SRIF receptor mRNAs [33].
  • However, IMD concentration-dependently inhibited GHRH-stimulated GH release from these cell cultures [34].
  • GHRH neurons coexpress the peptide galanin, but the functional significance of this coexpression is unknown [35].

Other interactions of Ghrh

  • Somatostatin had no measurable effect on the labeling index by itself, but it partly inhibited the GRF-induced increase in both the labeling index and the total number of cells [27].
  • We found that in the absence of furin (LoVo cells) or CHO cells treated with BFA, only one moiety was observed, and that corresponds to the same electrophorectic mobility to the GHRH precursor [36].
  • These findings suggest that the GHSs do not act by altering SRIF release but, rather, stimulate GH release via GHRH-dependent pathways [37].
  • The numbers of Fos-positive neurons and Fos-positive GHRH neurons in response to KP-102 were decreased in Tg rats [23].
  • These results indicate that thyroid hormone promotes pituitary GRF-R gene expression, not by modulating GRF secretion, but by acting on the pituitary directly [14].

Analytical, diagnostic and therapeutic context of Ghrh

  • 1. The effects of brief applications of growth hormone-releasing hormone (GHRH) to male rat somatotrophs in culture were analysed with the perforated patch clamp technique to record changes in potential or with fura-2 imaging techniques to measure variations of cytosolic Ca2+ concentration ([Ca2+]i) [18].
  • SS/GHRH increased following hypophysectomy and returned to control values by rGH replacement [2].
  • The rat has also been used extensively as an animal model to study the effects of GHRF on growth hormone synthesis and secretion and on somatic growth [11].
  • At 75 days of age, animals were killed, and in situ hybridization to detect GHRH and SS mRNA containing neurons was performed [38].
  • Repeated stimulation of pituitary cell cultures with GH-releasing hormone (GHRH) results in diminished responsiveness, a phenomenon referred to as homologous desensitization [39].


  1. Gene expression of hypothalamic somatostatin, growth hormone releasing factor, and their pituitary receptors in hypothyroidism. Tam, S.P., Lam, K.S., Srivastava, G. Endocrinology (1996) [Pubmed]
  2. Effect of hypophysectomy and growth hormone administration on hypothalamic growth hormone-releasing hormone and somatostatin content: relationship to age-related growth rate. Leidy, J.W., McDermott, M.T., Robbins, R.J. Neuroendocrinology (1990) [Pubmed]
  3. Interaction of growth hormone-releasing factor and somatostatin on ulcer healing and mucosal growth in rats: role of gastrin and epidermal growth factor. Konturek, S.J., Brzozowski, T., Dembinski, A., Warzecha, Z., Konturek, P.K., Yanaihara, N. Digestion (1988) [Pubmed]
  4. The effects of GH-releasing hormone/somatostatin on the 5'-promoter activity of the GH gene in vitro. Morishita, M., Iwasaki, Y., Onishi, A., Asai, M., Mutsuga, N., Yoshida, M., Oiso, Y., Inoue, K., Murohara, T. J. Mol. Endocrinol. (2003) [Pubmed]
  5. GH mRNA levels are elevated by forskolin but not GH releasing hormone in GHRH receptor-expressing MtT/S somatotroph cell line. Voss, T.C., Goldman, L.R., Seek, S.L., Miller, T.L., Mayo, K.E., Somogyvari-Vigh, A., Arimura, A., Hurley, D.L. Mol. Cell. Endocrinol. (2001) [Pubmed]
  6. The effect of REM sleep deprivation on somatostatin and growth hormone-releasing hormone gene expression in the rat hypothalamus. Toppila, J., Asikainen, M., Alanko, L., Turek, F.W., Stenberg, D., Porkka-Heiskanen, T. Journal of sleep research. (1996) [Pubmed]
  7. Antagonistic effects of growth hormone-releasing factor (GRF) and somatostatin on locomotor activity: GRF-induced hyperkinetic syndrome. Cacabelos, R., Niigawa, H., Alvarez, X.A., Muñoz, M.D., Nishimura, T., Rubia, F.J. Methods and findings in experimental and clinical pharmacology. (1990) [Pubmed]
  8. Influence of food deprivation in the rat on hypothalamic expression of growth hormone-releasing factor and somatostatin. Bruno, J.F., Olchovsky, D., White, J.D., Leidy, J.W., Song, J., Berelowitz, M. Endocrinology (1990) [Pubmed]
  9. Sleep deprivation increases somatostatin and growth hormone-releasing hormone messenger RNA in the rat hypothalamus. Toppila, J., Alanko, L., Asikainen, M., Tobler, I., Stenberg, D., Porkka-Heiskanen, T. Journal of sleep research. (1997) [Pubmed]
  10. Growth hormone-releasing factor (GRF) stimulates PGE2 production in rat anterior pituitary. Evidence for a PGE2 involvement in GRF-induced GH release. Fafeur, V., Gouin, E., Dray, F. Biochem. Biophys. Res. Commun. (1985) [Pubmed]
  11. Characterization of cDNA and genomic clones encoding the precursor to rat hypothalamic growth hormone-releasing factor. Mayo, K.E., Cerelli, G.M., Rosenfeld, M.G., Evans, R.M. Nature (1985) [Pubmed]
  12. Independent effects of growth hormone releasing factor on growth hormone release and gene transcription. Barinaga, M., Bilezikjian, L.M., Vale, W.W., Rosenfeld, M.G., Evans, R.M. Nature (1985) [Pubmed]
  13. Binding sites for growth hormone releasing factor on rat anterior pituitary cells. Seifert, H., Perrin, M., Rivier, J., Vale, W. Nature (1985) [Pubmed]
  14. Thyroid hormone regulation of gene expression of the pituitary growth hormone-releasing factor receptor. Miki, N., Ono, M., Murata, Y., Ohsaki, E., Tamitsu, K., Ri, T., Demura, H., Yamada, M. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  15. Protein kinase C enhances growth hormone releasing factor (1-40)-stimulated cyclic AMP levels in anterior pituitary. Actions of somatostatin and pertussis toxin. Cronin, M.J., Summers, S.T., Sortino, M.A., Hewlett, E.L. J. Biol. Chem. (1986) [Pubmed]
  16. Depletion of hypothalamic growth hormone-releasing hormone by neonatal monosodium glutamate treatment reveals an inhibitory effect of betamethasone on growth hormone secretion in adult rats. Corder, R., Saudan, P., Mazlan, M., McLean, C., Gaillard, R.C. Neuroendocrinology (1990) [Pubmed]
  17. Activation of ganglionic tyrosine hydroxylase by peptides of the secretin-glucagon family: structure-function studies. Schwarzschild, M.A., Vale, W., Corigliano-Murphy, A.C., Pisano, J.J., Ip, N.Y., Zigmond, R.E. Neuroscience (1989) [Pubmed]
  18. Growth hormone-releasing hormone triggers pacemaker activity and persistent Ca2+ oscillations in rat somatotrophs. Kwiecien, R., Tseeb, V., Kurchikov, A., Kordon, C., Hammond, C. J. Physiol. (Lond.) (1997) [Pubmed]
  19. Somatostatin desensitization in rat anterior pituitary cells. Smith, M.A., Yamamoto, G., Vale, W.W. Mol. Cell. Endocrinol. (1984) [Pubmed]
  20. Interleukin-1beta stimulates growth hormone-releasing hormone receptor mRNA expression in the rat hypothalamus in vitro and in vivo. Taishi, P., De, A., Alt, J., Gardi, J., Obal, F., Krueger, J.M. J. Neuroendocrinol. (2004) [Pubmed]
  21. Stimulation of mitogen-activated protein kinase pathway in rat somatotrophs by growth hormone-releasing hormone. Zeitler, P., Siriwardana, G. Endocrine (2000) [Pubmed]
  22. Somatostatin and growth hormone-releasing factor release from Zucker rat hypothalamic tissue. Giraudo, S.Q., Mullen, B.J., Seerley, R.W., Azain, M.J., Martin, R.J. Brain Res. Bull. (1992) [Pubmed]
  23. Growth hormone-releasing hormone (GHRH) neurons in the arcuate nucleus (Arc) of the hypothalamus are decreased in transgenic rats whose expression of ghrelin receptor is attenuated: Evidence that ghrelin receptor is involved in the up-regulation of GHRH expression in the arc. Mano-Otagiri, A., Nemoto, T., Sekino, A., Yamauchi, N., Shuto, Y., Sugihara, H., Oikawa, S., Shibasaki, T. Endocrinology (2006) [Pubmed]
  24. Regulational effect of ghrelin on growth hormone secretion from perifused rat anterior pituitary cells. Yamazaki, M., Nakamura, K., Kobayashi, H., Matsubara, M., Hayashi, Y., Kangawa, K., Sakai, T. J. Neuroendocrinol. (2002) [Pubmed]
  25. Regulation of 5'-Promoter Activity of the Rat Growth Hormone and Growth Hormone-Releasing Hormone Receptor Genes in the MtT/S and MtT/E Cells. Nogami, H., Hiraoka, Y., Inoue, K., Aiso, S., Hisano, S. Neuroendocrinology (2006) [Pubmed]
  26. Growth hormone-releasing factor regulation by somatostatin, growth hormone and insulin-like growth factor I in fetal rat hypothalamic-brain stem cell cocultures. Fernández Vázquez, G., Cacicedo, L., de los Frailes, M.T., Lorenzo, M.J., Tolón, R., Sánchez Franco, F. Neuroendocrinology (1993) [Pubmed]
  27. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro. Billestrup, N., Swanson, L.W., Vale, W. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  28. Somatostatin inhibits growth hormone-releasing factor-stimulated adenylate cyclase activity in GH, cells. Reyl-Desmars, F., Zeytin, F. Biochem. Biophys. Res. Commun. (1985) [Pubmed]
  29. The rat growth hormone-releasing hormone receptor gene: structure, regulation, and generation of receptor isoforms with different signaling properties. Miller, T.L., Godfrey, P.A., Dealmeida, V.I., Mayo, K.E. Endocrinology (1999) [Pubmed]
  30. Colocalization of somatostatin receptors and growth hormone-releasing factor immunoreactivity in neurons of the rat arcuate nucleus. McCarthy, G.F., Beaudet, A., Tannenbaum, G.S. Neuroendocrinology (1992) [Pubmed]
  31. Effect of insulin-like growth factor-I on growth hormone-releasing factor receptor expression in primary rat anterior pituitary cell culture. Sugihara, H., Emoto, N., Tamura, H., Kamegai, J., Shibasaki, T., Minami, S., Wakabayashi, I. Neurosci. Lett. (1999) [Pubmed]
  32. Expression and sexual dimorphism of galanin messenger ribonucleic acid in growth hormone-releasing hormone neurons of the rat during development. Delemarre-van de Waal, H.A., Burton, K.A., Kabigting, E.B., Steiner, R.A., Clifton, D.K. Endocrinology (1994) [Pubmed]
  33. Growth hormone-releasing hormone neurons in the arcuate nucleus express both Sst1 and Sst2 somatostatin receptor genes. Tannenbaum, G.S., Zhang, W.H., Lapointe, M., Zeitler, P., Beaudet, A. Endocrinology (1998) [Pubmed]
  34. Intermedin/Adrenomedullin-2 inhibits growth hormone release from cultured, primary anterior pituitary cells. Taylor, M.M., Bagley, S.L., Samson, W.K. Endocrinology (2006) [Pubmed]
  35. The role of galanin and its receptor in the feedback regulation of growth hormone secretion. Chan, Y.Y., Grafstein-Dunn, E., Delemarre-van de Waal, H.A., Burton, K.A., Clifton, D.K., Steiner, R.A. Endocrinology (1996) [Pubmed]
  36. Stepwise posttranslational processing of progrowth hormone-releasing hormone (proGHRH) polypeptide by furin and PC1. Posner, S.F., Vaslet, C.A., Jurofcik, M., Lee, A., Seidah, N.G., Nillni, E.A. Endocrine (2004) [Pubmed]
  37. Interactions of growth hormone secretagogues and growth hormone-releasing hormone/somatostatin. Tannenbaum, G.S., Bowers, C.Y. Endocrine (2001) [Pubmed]
  38. Differential effects of the neonatal and adult sex steroid environments on the organization and activation of hypothalamic growth hormone-releasing hormone and somatostatin neurons. Chowen, J.A., Argente, J., González-Parra, S., García-Segura, L.M. Endocrinology (1993) [Pubmed]
  39. Homologous down-regulation of growth hormone-releasing hormone receptor messenger ribonucleic acid levels. Aleppo, G., Moskal, S.F., De Grandis, P.A., Kineman, R.D., Frohman, L.A. Endocrinology (1997) [Pubmed]
WikiGenes - Universities