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Gene Review

GH  -  growth hormone

Ovis aries

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Disease relevance of GH

  • We have previously reported (Bauer MK, Breier BH, Bloomfield FH, Jensen EC, Gluckman PD, and Harding JE. J Endocrinol 177: 83-92, 2003) that a chronic pulsatile infusion of growth hormone (GH) to intrauterine growth-restricted (IUGR) ovine fetuses increased fetal circulating IGF-I levels without increasing fetal growth [1].
  • Insulin hypoglycemia resulted in a rapid and brief stimulation of SRIH secretion followed by a decline in GH levels [2].
  • Thus, chronic hypoxemia in the newborn is associated with a decrease in IGF-I and IGFBP-3 in the face of normal GH [3].
  • This suggests peripheral GH unresponsiveness, similar to protein-calorie malnutrition or GH receptor deficiency dwarfism, but mediated at a level distal to the hepatic GH receptor [3].
  • Feeding, distention of the rumen and anticipation of being fed each reduced (P less than 0.05) the GH response to intravenous injection of 0.067 micrograms GHRF/kg body weight [4].

Psychiatry related information on GH

  • Trials were conducted to determine the influence of feed and water deprivation on feed intake, plasma glucose, free fatty acids (FFA), urea-N (PUN), serum insulin and growth hormone (GH) in lambs [5].

High impact information on GH

  • The purified receptor bound 125I-oPL specifically and with high affinity (Kd 0.5 nM) but did not bind either radiolabeled ovine GH or ovine PRL [6].
  • The GH inhibitory effect required the tyrosine phosphorylation site (Tyr-699) of STAT5b, an intact STAT5b DNA binding domain, and the presence of a COOH-terminal trans-activation domain [7].
  • Hepatic peroxisome proliferation induced by structurally diverse non-genotoxic carcinogens is mediated by the nuclear receptor peroxisome proliferator-activated receptor (PPARalpha) and can be inhibited by growth hormone (GH) [7].
  • Serum was collected on days 28, 73, 118, 135, and 163 and analyzed for minerals (Ca, P, and Mg), markers of bone remodeling (bone alkaline phosphatase [ALP] and tartrate resistant acid phosphatase [TRAP]), 1,25-dihydroxyvitamin D [1,25(OH)2D], growth hormone (GH), and insulin-like growth factor I (IGF-I) [8].
  • These results suggest that the inhibition of Kir current through PKA-cAMP pathways may play an integral role in GHRP-2-induced depolarisation and GH release in ovine somatotropes [9].

Chemical compound and disease context of GH

  • In conclusion, the modest increases in circulating cortisol concentrations in IUGR fetuses did not increase hepatic GH-R mRNA expression and, therefore, do not explain the increased circulating IGF-I levels that we found with GH infusion, which are likely due to reduced clearance rather than increased production [1].
  • Insulin-induced hypoglycemia inhibited GRF effects on plasma GH concentrations while glucose infusion enhanced bGRF actions [10].
  • The ability of GH to modulate the PIA-activated adenosine receptor to stimulate dissociation of heterotrimeric Gi was assessed by measurement of pertussis toxin-catalysed ADP-ribosylation of Gi; GH does not appear to alter the interaction between the activated receptor and Gi [11].
  • Further studies on DNCB contact sensitivity and on antibody formation revealed that the immunocompetence of BRC-suppressed animals could be restored by additional treatment with either prolactin (PRL) or growth hormone (GH) [12].

Biological context of GH

  • We demonstrate tissue-specific regulation of the somatotrophic axis in IUGR fetuses and a discontinuity between GH-R and IGF-I gene expression in GH-infused fetuses that is not explained by alterations in phosphorylated STAT5b [1].
  • The sequence for the sheep growth hormone (GH) is in agreement with the amino acid sequence of the protein determined previously except for the asparagine residue at position 99 rather than aspartic acid and the arginine residue at position 146 in place of threonine [13].
  • This dose of IGF-I had no effect on GRF (10(-9) M)-stimulated GH release at 70 days gestation [14].
  • In conclusion, exogenous GH has profound effects on maternal endocrinology, metabolism, and body composition when administered during early and late pregnancy [15].
  • Although administration of exogenous gonadotropins stimulates follicular growth and ovulation in HPD ewes, follicles in HPX ewes remain unresponsive unless growth hormone (GH) is also given [16].

Anatomical context of GH

  • In umbilical blood, however, GH was detected from d35 and was presumed to be of placental origin, because GH mRNA was not detected in the fetal pituitary gland on d40 [17].
  • GH mRNA was localized in the trophectoderm and syncytium [17].
  • The results of this study indicate that between d35-d50 of pregnancy, the endometrium, placenta, and fetus are all potential targets for the placental GH [17].
  • Moreover, this specific effect of high K(+) on the Kir current was only observed in the cells that showed positive staining with anti-growth hormone (GH) antibodies, or in GC cells that belong to a rat somatotrope cell line [9].
  • The levels of mRNA for GH in pituitary cytosol were increased by restricted feeding, but no changes were seen in mRNA levels of alpha-subunit, LH beta, FSH beta, or PRL [18].

Associations of GH with chemical compounds

  • The predicted sequence for ovine GH agrees with that determined previously on the protein, except that residue 99 is asparagine rather than aspartic acid [19].
  • An increase in jugular GH levels was observed 15 min after hexarelin injection (9.1 +/- 1.8 vs. 3.9 +/- 0.8 ng/ml; P < 0.05) [20].
  • Injection of SRIF antiserum (oA-SRIF) increases serum GH and TSH levels in urethane-anesthetized rats [21].
  • The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity [22].
  • GH administration elevated maternal plasma concentrations of GH, insulin, glucose, and nonesterified fatty acids during the defined treatment windows, while urea concentrations were decreased [15].

Physical interactions of GH


Regulatory relationships of GH

  • We conclude that TNF alpha can regulate both GH and IL-6 synthesis in dispersed ovine pituitary cells [24].
  • Moreover, 10(-7) M SRIF blocked the stimulation of GH secretion induced by 10(-8) M GRF [25].
  • Many of the anabolic effects of growth hormone (GH) are indirect, occurring through GH-stimulated production of insulin-like growth factor-I (IGF-I) by the liver [26].
  • In the absence of other hormones GH had no effect on either the expressed (initial) or total activity of acetyl-CoA carboxylase, but GH prevented the increase in both expressed and total activities of the enzyme induced by insulin plus dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)[27]
  • These results suggest that leptin has a long-term effect on somatotrophs to reduce GHRH receptor synthesis leading to a decrease in GHRH-stimulated GH secretion [28].

Other interactions of GH

  • IUGR increased hepatic IGF-binding protein (IGFBP)-1 and placental IGFBP-2 and -3 mRNA levels with no further effect of GH infusion [1].
  • TNF alpha at concentrations between 1-1000 U/ml increased GH and IL-6 mRNA, relative to control levels, by 5 h post-stimulation [24].
  • Pulses of SRIF were not significantly associated with changes in GH or GRF concentrations [29].
  • This experiment evaluated relationships between pituitary messenger RNA levels of the transcription factor Pit-1, the growth hormone releasing-hormone receptor (GHRHR), and synthesis and secretion of GH in growing wethers [30].
  • Ovine placental lactogen is a potent somatogen in the growth hormone (GH)-deficient rat: comparison of somatogenic activity with bovine GH [31].

Analytical, diagnostic and therapeutic context of GH

  • Northern blot analysis of placental RNA showed the expression of GH-hybridizing transcripts migrating to the same position as that of GH pituitary messenger RNA (mRNA) [32].
  • Their sequence analysis showed the existence of three GH mRNA (GHP1, GHP2, and GHP3) [32].
  • GH-like immunoreactivity was localized on cotyledonary frozen sections in the syncytium and the trophectoderm [32].
  • Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M(r) range of 7,000 to 55,000 [22].
  • The presence of GH and PRL was determined by SDS-PAGE and Western blots [33].


  1. Effect of pulsatile growth hormone administration to the growth-restricted fetal sheep on somatotrophic axis gene expression in fetal and placental tissues. Bloomfield, F.H., van Zijl, P.L., Bauer, M.K., Phua, H.H., Harding, J.E. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  2. Measurement of growth hormone-releasing hormone and somatostatin in hypothalamic-portal plasma of unanesthetized sheep. Spontaneous secretion and response to insulin-induced hypoglycemia. Frohman, L.A., Downs, T.R., Clarke, I.J., Thomas, G.B. J. Clin. Invest. (1990) [Pubmed]
  3. Decreased serum insulin-like growth factor-I associated with growth failure in newborn lambs with experimental cyanotic heart disease. Bernstein, D., Jasper, J.R., Rosenfeld, R.G., Hintz, R.L. J. Clin. Invest. (1992) [Pubmed]
  4. Influence of feeding on growth hormone secretion and response to growth hormone-releasing factor in sheep. Trenkle, A. J. Nutr. (1989) [Pubmed]
  5. Influence of fasting and post-fast diet energy level on feed intake, feeding pattern and blood variables of lambs. Cole, N.A., Purdy, C.W., Hallford, D.M. J. Anim. Sci. (1988) [Pubmed]
  6. Purification of a distinct placental lactogen receptor, a new member of the growth hormone/prolactin receptor family. Freemark, M., Comer, M. J. Clin. Invest. (1989) [Pubmed]
  7. Cross-talk between janus kinase-signal transducer and activator of transcription (JAK-STAT) and peroxisome proliferator-activated receptor-alpha (PPARalpha) signaling pathways. Growth hormone inhibition of pparalpha transcriptional activity mediated by stat5b. Zhou, Y.C., Waxman, D.J. J. Biol. Chem. (1999) [Pubmed]
  8. Estrogen agonist (zeranol) treatment in a castrated male lamb model: effects on growth and bone mineral accretion. Chanetsa, F., Hillman, L.S., Thomas, M.G., Keisler, D.H. J. Bone Miner. Res. (2000) [Pubmed]
  9. Growth hormone-releasing peptide-2 reduces inward rectifying K+ currents via a PKA-cAMP-mediated signalling pathway in ovine somatotropes. Xu, R., Zhao, Y., Chen, C. J. Physiol. (Lond.) (2002) [Pubmed]
  10. Modulation of growth hormone-releasing factor stimulated growth hormone secretion by plasma glucose and free fatty acid concentrations in sheep. Sartin, J.L., Bartol, F.F., Kemppainen, R.J., Dieberg, G., Buxton, D., Soyoola, E. Neuroendocrinology (1988) [Pubmed]
  11. Regulation of the GTP-binding protein-based antilipolytic system of sheep adipocytes by growth hormone. Doris, R.A., Kilgour, E., Houslay, M.D., Vernon, R.G. J. Endocrinol. (1998) [Pubmed]
  12. Immunomodulation by bromocriptine. Nagy, E., Berczi, I., Wren, G.E., Asa, S.L., Kovacs, K. Immunopharmacology (1983) [Pubmed]
  13. Cloning and nucleotide sequencing of sheep growth hormone cDNA. Guron, C., Rao, K.B., Jain, S.K., Totey, S.M., Talwar, G.P. Indian J. Exp. Biol. (1992) [Pubmed]
  14. In vitro regulation of growth hormone (GH) release from ovine pituitary cells during fetal and neonatal development: effects of GH-releasing factor, somatostatin, and insulin-like growth factor I. Blanchard, M.M., Goodyer, C.G., Charrier, J., Barenton, B. Endocrinology (1988) [Pubmed]
  15. Late but not early gestational maternal growth hormone treatment increases fetal adiposity in overnourished adolescent sheep. Wallace, J.M., Matsuzaki, M., Milne, J., Aitken, R. Biol. Reprod. (2006) [Pubmed]
  16. Localization and quantification of binding sites for follicle-stimulating hormone, luteinizing hormone, growth hormone, and insulin-like growth factor I in sheep ovarian follicles. Eckery, D.C., Moeller, C.L., Nett, T.M., Sawyer, H.R. Biol. Reprod. (1997) [Pubmed]
  17. Expression of growth hormone and its receptor in the placental and feto-maternal environment during early pregnancy in sheep. Lacroix, M.C., Devinoy, E., Cassy, S., Servely, J.L., Vidaud, M., Kann, G. Endocrinology (1999) [Pubmed]
  18. Effect of restricted feeding on the concentrations of growth hormone (GH), gonadotropins, and prolactin (PRL) in plasma, and on the amounts of messenger ribonucleic acid for GH, gonadotropin subunits, and PRL in the pituitary glands of adult ovariectomized ewes. Thomas, G.B., Mercer, J.E., Karalis, T., Rao, A., Cummins, J.T., Clarke, I.J. Endocrinology (1990) [Pubmed]
  19. Cloning, sequence and expression in Escherichia coli of cDNA for ovine pregrowth hormone. Warwick, J.M., Wallis, O.C., Wallis, M. Biochim. Biophys. Acta (1989) [Pubmed]
  20. Growth hormone (GH)-releasing hormone secretion is stimulated by a new GH-releasing hexapeptide in sheep. Guillaume, V., Magnan, E., Cataldi, M., Dutour, A., Sauze, N., Renard, M., Razafindraibe, H., Conte-Devolx, B., Deghenghi, R., Lenaerts, V. Endocrinology (1994) [Pubmed]
  21. Antiserum to rat growth hormone (GH)-releasing factor suppresses but does not abolish antisomatostatin-induced GH release in the rat. Thomas, C.R., Groot, K., Arimura, A. Endocrinology (1985) [Pubmed]
  22. Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland. Noteborn, H.P., van Balen, P.P., van der Gugten, A.A., Hart, I.C., Ebels, I., Salemink, C.A. J. Pineal Res. (1993) [Pubmed]
  23. Effect of high-protein feed supplements on concentrations of growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in plasma and on the amounts of GH and messenger RNA for GH in the pituitary glands of adult rams. Clarke, I.J., Fletcher, T.P., Pomares, C.C., Holmes, J.H., Dunshea, F., Thomas, G.B., Tilbrook, A.J., Walton, P.E., Galloway, D.B. J. Endocrinol. (1993) [Pubmed]
  24. Effects of tumour necrosis factor-alpha on growth hormone and interleukin 6 mRNA in ovine pituitary cells. Nash, A.D., Brandon, M.R., Bello, P.A. Mol. Cell. Endocrinol. (1992) [Pubmed]
  25. Effects of hypothalamic hormones (GRF, TRH, somatostatin) and insulin-like growth factor I on growth hormone secretion from prepubertal male lamb pituitary cultures. Blanchard, M.M., Goodyer, C.G., Charrier, J., Dulor, J.P., Barenton, B. Reproduction, nutrition, development. (1987) [Pubmed]
  26. Growth hormone and amino acid supply interact synergistically to control insulin-like growth factor-I production and gene expression in cultured ovine hepatocytes. Wheelhouse, N.M., Stubbs, A.K., Lomax, M.A., MacRae, J.C., Hazlerigg, D.G. J. Endocrinol. (1999) [Pubmed]
  27. Growth hormone inhibition of lipogenesis in sheep adipose tissue: requirement for gene transcription and polyamines. Borland, C.A., Barber, M.C., Travers, M.T., Vernon, R.G. J. Endocrinol. (1994) [Pubmed]
  28. The in vitro effect of leptin on growth hormone secretion from primary cultured ovine somatotrophs. Chen, C., Roh, S.G., Nie, G.Y., Loneragan, K., Xu, R.W., Ruan, M., Clarke, L.J., Goding, J.W., Gertler, A. Endocrine (2001) [Pubmed]
  29. Effect of restricted feeding on the relationship between hypophysial portal concentrations of growth hormone (GH)-releasing factor and somatostatin, and jugular concentrations of GH in ovariectomized ewes. Thomas, G.B., Cummins, J.T., Francis, H., Sudbury, A.W., McCloud, P.I., Clarke, I.J. Endocrinology (1991) [Pubmed]
  30. Transcriptional regulation of pituitary synthesis and secretion of growth hormone in growing wethers and the influence of zeranol on these mechanisms. Thomas, M.G., Carroll, J.A., Raymond, S.R., Matteri, R.L., Keisler, D.H. Domest. Anim. Endocrinol. (2000) [Pubmed]
  31. Ovine placental lactogen is a potent somatogen in the growth hormone (GH)-deficient rat: comparison of somatogenic activity with bovine GH. Singh, K., Ambler, G.R., Breier, B.H., Klempt, M., Gluckman, P.D. Endocrinology (1992) [Pubmed]
  32. Expression of the growth hormone gene in ovine placenta: detection and cellular localization of the protein. Lacroix, M.C., Devinoy, E., Servely, J.L., Puissant, C., Kann, G. Endocrinology (1996) [Pubmed]
  33. Partial purification and characterization of rhinoceros gonadotropins, growth hormone, and prolactin: comparison with the horse and sheep. McFarlane, J.R., Cabrera, C.M., Coulson, S.A., Papkoff, H. Biol. Reprod. (1991) [Pubmed]
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