Abstract
Like many other neuroendocrine hormones, growth hormone (GH; somatotropin) secretion is pulsatile with regular releasing bursts on a relatively low constitutive basal secretion. This chapter discusses current knowledge of the regulation and the function of GH pulsatile profiles, with new development of laboratory approaches and introduces knowledge about GH functions on metabolic regulation in addition to the conventional concept of a role in regulating body growth. As reported in the literature, amplitude, frequency, and regularity of GH secretion are tightly linked to metabolic conditions with clear species and gender differences. In response to negative and positive energy balances, the GH pulsatile pattern changes to mobilize or store energy in adipose, muscle, and liver in order to accommodate the changing nutritional conditions. Changes in GH pulsatility are achieved through regulating the hypothalamo–pituitary GH axis with altered levels of key stimulatory and inhibitory hormones, GH-releasing hormone (GHRH) and somatostatin (SRIF, somatotropin release inhibiting factor). The hypothalamic–pituitary GH axis is constantly under the influence of peripheral metabolic factors, such as lipid and glucose levels; peripheral metabolic regulatory hormones, such as leptin and insulin; and central metabolic regulatory neuropeptides, such as neuropeptide Y and melanocortin. Regulation of the hypothalamic–pituitary GH axis is achieved through activation of cell membrane receptors, intracellular signaling pathways, and membrane ion channels. Detailed regulatory mechanisms are discussed in this chapter in order to understand the coupling of cell electrophysiological properties and the hormone secretory process of exocytosis in hypothalamic neurons and pituitary GH-secreting somatotrophs. Technical advances in electrophysiology, cell imaging analysis, and real-time in vivo hormone analysis are discussed to deepen the understanding of physiological and pathophysiological regulation of GH secretion. Future directions are also discussed, as are unanswered questions in this field.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Albertsson-Wikland K, Rosberg S (1988) Analyses of 24-hour growth hormone profiles in children: relation to growth. J Clin Endocrinol Metab 67(3):493–500. https://doi.org/10.1210/jcem-67-3-493
Aydin S (2015) A short history, principles, and types of ELISA, and our laboratory experience with peptide/protein analyses using ELISA. Peptides 72:4–15. https://doi.org/10.1016/j.peptides.2015.04.012
Balthasar N, Mery PF, Magoulas CB, Mathers KE, Martin A, Mollard P, Robinson IC (2003) Growth hormone-releasing hormone (GHRH) neurons in GHRH-enhanced green fluorescent protein transgenic mice: a ventral hypothalamic network. Endocrinology 144(6):2728–2740. https://doi.org/10.1210/en.2003-0006
Basgut B, Kayki G, Bartosova L, Ozakca I, Seymen A, Kandilci HB, Ugur M, Turan B, Ozcelikay AT (2010) Cardioprotective effects of 44Bu, a newly synthesized compound, in rat heart subjected to ischemia/reperfusion injury. Eur J Pharmacol 640(1–3):117–123. https://doi.org/10.1016/j.ejphar.2010.04.045
Bassett JM (1974) Diurnal patterns of plasma insulin, growth hormone, corticosteroid and metabolite concentrations in fed and fasted sheep. Aust J Biol Sci 27(2):167–181
Bauer MK, Harding JE, Bassett NS, Breier BH, Oliver MH, Gallaher BH, Evans PC, Woodall SM, Gluckman PD (1998) Fetal growth and placental function. Mol Cell Endocrinol 140(1–2):115–120
Binnerts A, Swart GR, Wilson JH, Hoogerbrugge N, Pols HA, Birkenhager JC, Lamberts SW (1992) The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition. Clin Endocrinol 37(1):79–87
Blackard WG, Hull EW, Lopez A (1971) Effect of lipids on growth hormone secretion in humans. J Clin Invest 50(7):1439–1443. https://doi.org/10.1172/JCI106627
Bonnefont X, Mollard P (2003) Electrical activity in endocrine pituitary cells in situ: a support for a multiple-function coding. FEBS Lett 548(1–3):49–52
Bonnefont X, Fiekers J, Creff A, Mollard P (2000) Rhythmic bursts of calcium transients in acute anterior pituitary slices. Endocrinology 141(3):868–875. https://doi.org/10.1210/endo.141.3.7363
Bonnefont X, Lacampagne A, Sanchez-Hormigo A, Fino E, Creff A, Mathieu MN, Smallwood S, Carmignac D, Fontanaud P, Travo P, Alonso G, Courtois-Coutry N, Pincus SM, Robinson IC, Mollard P (2005) Revealing the large-scale network organization of growth hormone-secreting cells. Proc Natl Acad Sci USA 102(46):16880–16885. https://doi.org/10.1073/pnas.0508202102
Breier BH, Bass JJ, Butler JH, Gluckman PD (1986) The somatotrophic axis in young steers: influence of nutritional status on pulsatile release of growth hormone and circulating concentrations of insulin-like growth factor 1. J Endocrinol 111(2):209–215
Cai A, Hyde JF (1999) The human growth hormone-releasing hormone transgenic mouse as a model of modest obesity: differential changes in leptin receptor (OBR) gene expression in the anterior pituitary and hypothalamus after fasting and OBR localization in somatotrophs. Endocrinology 140(8):3609–3614. https://doi.org/10.1210/endo.140.8.6925
Cerda-Reverter JM, Larhammar D (2000) Neuropeptide Y family of peptides: structure, anatomical expression, function, and molecular evolution. Biochem Cell Biol 78(3):371–392
Cersosimo E, Danou F, Persson M, Miles JM (1996) Effects of pulsatile delivery of basal growth hormone on lipolysis in humans. Am J Phys 271(1 Pt 1):E123–E126
Chen C (2002) The effect of two-day treatment of primary cultured ovine somatotropes with GHRP-2 on membrane voltage-gated K+ currents. Endocrinology 143(7):2659–2663. https://doi.org/10.1210/endo.143.7.8916
Chen C, Clarke IJ (1992) Ion channels in the regulation of growth hormone secretion from somatotrophs by somatostatin. Growth Regul 2(4):167–174
Chen C, Clarke IJ (1995a) Effects of growth hormone-releasing peptide-2 (GHRP-2) on membrane Ca2+ permeability in cultured ovine somatotrophs. J Neuroendocrinol 7(3):179–186
Chen C, Clarke IJ (1995b) Modulation of Ca2+ influx in the ovine somatotroph by growth hormone-releasing factor. Am J Phys 268(2 Pt 1):E204–E212
Chen C, Clarke IJ (1996) G(o)-2 protein mediates the reduction in Ca2+ currents by somatostatin in cultured ovine somatotrophs. J Physiol 491(Pt 1):21–29
Chen C, Israel JM, Vincent JD (1989a) Electrophysiological responses of rat pituitary cells in somatotroph-enriched primary culture to human growth-hormone releasing factor. Neuroendocrinology 50(6):679–687
Chen C, Israel JM, Vincent JD (1989b) Electrophysiological responses to somatostatin of rat hypophysial cells in somatotroph-enriched primary cultures. J Physiol 408:493–510
Chen C, Zhang J, Vincent JD, Israel JM (1990a) Sodium and calcium currents in action potentials of rat somatotrophs: their possible functions in growth hormone secretion. Life Sci 46(14):983–989
Chen C, Zhang J, Vincent JD, Israel JM (1990b) Somatostatin increases voltage-dependent potassium currents in rat somatotrophs. Am J Phys 259(6 Pt 1):C854–C861
Chen C, Zhang J, Vincent JD, Israel JM (1990c) Two types of voltage-dependent calcium current in rat somatotrophs are reduced by somatostatin. J Physiol 425:29–42
Chen C, Heyward P, Zhang J, Wu D, Clarke IJ (1994a) Voltage-dependent potassium currents in ovine somatotrophs and their function in growth hormone secretion. Neuroendocrinology 59(1):1–9
Chen C, Vincent JD, Clarke IJ (1994b) Ion channels and the signal transduction pathways in the regulation of growth hormone secretion. Trends Endocrinol Metab 5(6):227–233
Chen C, Xu R, Clarke IJ, Ruan M, Loneragan K, Roh SG (2000) Diverse intracellular signalling systems used by growth hormone-releasing hormone in regulating voltage-gated Ca2+ or K channels in pituitary somatotropes. Immunol Cell Biol 78(4):356–368. https://doi.org/10.1046/j.1440-1711.2000.00917.x
Clark RG, Carlsson LM, Robinson IC (1987) Growth hormone secretory profiles in conscious female rats. J Endocrinol 114(3):399–407
Clasey JL, Weltman A, Patrie J, Weltman JY, Pezzoli S, Bouchard C, Thorner MO, Hartman ML (2001) Abdominal visceral fat and fasting insulin are important predictors of 24-hour GH release independent of age, gender, and other physiological factors. J Clin Endocrinol Metab 86(8):3845–3852. https://doi.org/10.1210/jcem.86.8.7731
Cornford AS, Barkan AL, Horowitz JF (2011) Rapid suppression of growth hormone concentration by overeating: potential mediation by hyperinsulinemia. J Clin Endocrinol Metab 96(3):824–830. https://doi.org/10.1210/jc.2010-1895
Cornford AS, Barkan AL, Hinko A, Horowitz JF (2012) Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk. Am J Physiol Endocrinol Metab 303(10):E1264–E1272. https://doi.org/10.1152/ajpendo.00320.2012
Daikoku S, Hisano S, Kawano H, Chikamori-Aoyama M, Kagotani Y, Zhang RJ, Chihara K (1988) Ultrastructural evidence for neuronal regulation of growth hormone secretion. Neuroendocrinology 47(5):405–415
Department of Health: About Overweight and Obesity (2009). http://www.health.gov.au/internet/main/publishing.nsf/content/health-pubhlth-strateg-hlthwt-obesity.htm
Dhir RN, Shapiro BH (2003) Interpulse growth hormone secretion in the episodic plasma profile causes the sex reversal of cytochrome P450s in senescent male rats. Proc Natl Acad Sci USA 100(25):15224–15228. https://doi.org/10.1073/pnas.2434273100
Diamond FB, Jorgensen EV, Root AW, Shulman DI, Sy JP, Blethen SL, Bercu BB (1998) The role of serial sampling in the diagnosis of growth hormone deficiency. Pediatrics 102(2 Pt 3):521–524
Dimaraki EV, Jaffe CA (2006) Role of endogenous ghrelin in growth hormone secretion, appetite regulation and metabolism. Rev Endocr Metab Disord 7(4):237–249. https://doi.org/10.1007/s11154-006-9022-0
Engvall E, Perlmann P (1971) Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry 8(9):871–874
Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential csells from mouse embryos. Nature 292(5819):154–156
Felig P, Marliss EB, Cahill GF Jr (1971) Metabolic response to human growth hormone during prolonged starvation. J Clin Invest 50(2):411–421. https://doi.org/10.1172/JCI106508
Gahete MD, Cordoba-Chacon J, Lin Q, Bruning JC, Kahn CR, Castano JP, Christian H, Luque RM, Kineman RD (2013) Insulin and IGF-I inhibit GH synthesis and release in vitro and in vivo by separate mechanisms. Endocrinology 154(7):2410–2420. https://doi.org/10.1210/en.2013-1261
Galgani J, Ravussin E (2008) Energy metabolism, fuel selection and body weight regulation. Int J Obes (Lond) 32(Suppl 7):S109–S119. https://doi.org/10.1038/ijo.2008.246
Giustina A, Veldhuis JD (1998) Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 19(6):717–797. https://doi.org/10.1210/edrv.19.6.0353
Guerineau N, Drouhault R, Corcuff JB, Vacher AM, Vilayleck N, Mollard P (1990) Galanin evokes a cytosolic calcium bursting mode and hormone release in GH3/B6 pituitary cells. FEBS Lett 276(1–2):111–114
Guerineau NC, Bonnefont X, Stoeckel L, Mollard P (1998) Synchronized spontaneous Ca2+ transients in acute anterior pituitary slices. J Biol Chem 273(17):10389–10395
Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391(2):85–100
Han XF, Zhu YL, Hernandez M, Keating DJ, Chen C (2005) Ghrelin reduces voltage-gated potassium currents in GH3 cells via cyclic GMP pathways. Endocrine 28(2):217–224. https://doi.org/10.1385/endo:28:2:217
Han X, Zhu Y, Zhao Y, Chen C (2011) Ghrelin reduces voltage-gated calcium currents in GH(3) cells via cyclic GMP pathways. Endocrine 40(2):228–236. https://doi.org/10.1007/s12020-011-9520-z
Hansen TK, Jorgensen JO, Christiansen JS (2002) Body composition and circulating levels of insulin, insulin-like growth factor-binding protein-1 and growth hormone (GH)-binding protein affect the pharmacokinetics of GH in adults independently of age. J Clin Endocrinol Metab 87(5):2185–2193. https://doi.org/10.1210/jcem.87.5.8473
Hartmann BW, Kirchengast S, Albrecht AE, Soregi G, Huber JC (1996) Altered growth hormone (GH) secretion in women gaining weight during hormone replacement therapy (HRT). Maturitas 25(1):29–34
Hattori K, Shirasawa N, Suzuki H, Otsuka T, Wada I, Yashiro T, Herbert DC, Soji T, Hashitani H (2013) Intercellular communication within the rat anterior pituitary gland. XV. Properties of spontaneous and LHRH-induced Ca2+ transients in the transitional zone of the rat anterior pituitary in situ. Endocrinology 154(1):400–409. https://doi.org/10.1210/en.2012-1501
Ho KY, Veldhuis JD, Johnson ML, Furlanetto R, Evans WS, Alberti KG, Thorner MO (1988) Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man. J Clin Invest 81(4):968–975. https://doi.org/10.1172/JCI113450
Holl RW, Thorner MO, Leong DA (1988) Intracellular calcium concentration and growth hormone secretion in individual somatotropes: effects of growth hormone-releasing factor and somatostatin. Endocrinology 122(6):2927–2932. https://doi.org/10.1210/endo-122-6-2927
Holl RW, Hartman ML, Veldhuis JD, Taylor WM, Thorner MO (1991) Thirty-second sampling of plasma growth hormone in man: correlation with sleep stages. J Clin Endocrinol Metab 72(4):854–861. https://doi.org/10.1210/jcem-72-4-854
Horvath S, Palkovits M, Gorcs T, Arimura A (1989) Electron microscopic immunocytochemical evidence for the existence of bidirectional synaptic connections between growth hormone-releasing hormone- and somatostatin-containing neurons in the hypothalamus of the rat. Brain Res 481(1):8–15
Howell OW, Scharfman HE, Herzog H, Sundstrom LE, Beck-Sickinger A, Gray WP (2003) Neuropeptide Y is neuroproliferative for post-natal hippocampal precursor cells. J Neurochem 86(3):646–659
Huang L, Steyn FJ, Tan HY, Xie TY, Veldhuis JD, Ngo ST, Chen C (2012) The decline in pulsatile GH secretion throughout early adulthood in mice is exacerbated by dietary-induced weight gain. Endocrinology 153(9):4380–4388. https://doi.org/10.1210/en.2012-1178
Huang L, Tan HY, Fogarty MJ, Andrews ZB, Veldhuis JD, Herzog H, Steyn FJ, Chen C (2014) Actions of NPY, and its Y1 and Y2 receptors on pulsatile growth hormone secretion during the fed and fasted state. J Neurosci 34(49):16309–16319. https://doi.org/10.1523/JNEUROSCI.4622-13.2014
Husman B, Gustafsson JA, Andersson G (1988) Receptor-mediated endocytosis and degradation of bovine growth hormone in rat liver. Mol Cell Endocrinol 59(1–2):13–25
Inagaki T, Lin VY, Goetz R, Mohammadi M, Mangelsdorf DJ, Kliewer SA (2008) Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. Cell Metab 8(1):77–83. https://doi.org/10.1016/j.cmet.2008.05.006
Iranmanesh A, Lizarralde G, Veldhuis JD (1991) Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 73(5):1081–1088. https://doi.org/10.1210/jcem-73-5-1081
Karl T, Duffy L, Herzog H (2008) Behavioural profile of a new mouse model for NPY deficiency. Eur J Neurosci 28(1):173–180. https://doi.org/10.1111/j.1460-9568.2008.06306.x
Kidokoro Y (1975) Developmental changes of membrane electrical properties in a rat skeletal muscle cell line. J Physiol 244(1):129–143
Kohler C, Smialowska M, Eriksson LG, Chanpalay V, Davies S (1986) Origin of the neuropeptide Y innervation of the rat retrohippocampal region. Neurosci Lett 65(3):287–292
Kristrom B, Lofqvist C, Rosberg S, Albertsson Wikland K (2001) Effect of spontaneous GH secretion and the GH sampling period on the accuracy of models for predicting growth responses to GH treatment. J Clin Endocrinol Metab 86(10):4963–4964. https://doi.org/10.1210/jcem.86.10.7945
Kushler RH, Brown MB (1991) A model for the identification of hormone pulses. Stat Med 10(3):329–340
Kwiecien R, Hammond C (1998) Differential management of Ca2+ oscillations by anterior pituitary cells: a comparative overview. Neuroendocrinology 68(3):135–151
Kwiecien R, Robert C, Cannon R, Vigues S, Arnoux A, Kordon C, Hammond C (1998) Endogenous pacemaker activity of rat tumour somatotrophs. J Physiol 508(Pt 3):883–905
Lanes R (1989) Diagnostic limitations of spontaneous growth hormone measurements in normally growing prepubertal children. Am J Dis Child 143(11):1284–1286
Li CH, Papkoff H (1956) Preparation and properties of growth hormone from human and monkey pituitary glands. Science 124(3235):1293–1294
Liposits Z, Merchenthaler I, Paull WK, Flerko B (1988) Synaptic communication between somatostatinergic axons and growth hormone-releasing factor (GRF) synthesizing neurons in the arcuate nucleus of the rat. Histochemistry 89(3):247–252
Luque RM, Huang ZH, Shah B, Mazzone T, Kineman RD (2007) Effects of leptin replacement on hypothalamic-pituitary growth hormone axis function and circulating ghrelin levels in ob/ob mice. Am J Physiol Endocrinol Metab 292(3):E891–E899. https://doi.org/10.1152/ajpendo.00258.2006
MacLeod JN, Worsley I, Ray J, Friesen HG, Liebhaber SA, Cooke NE (1991) Human growth hormone-variant is a biologically active somatogen and lactogen. Endocrinology 128(3):1298–1302. https://doi.org/10.1210/endo-128-3-1298
Magoulas C, McGuinness L, Balthasar N, Carmignac DF, Sesay AK, Mathers KE, Christian H, Candeil L, Bonnefont X, Mollard P, Robinson IC (2000) A secreted fluorescent reporter targeted to pituitary growth hormone cells in transgenic mice. Endocrinology 141(12):4681–4689. https://doi.org/10.1210/endo.141.12.7828
Martinelli CE, Keogh JM, Greenfield JR, Henning E, van der Klaauw AA, Blackwood A, O’Rahilly S, Roelfsema F, Camacho-Hubner C, Pijl H, Farooqi IS (2011) Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with increased linear growth and final height, fasting hyperinsulinemia, and incompletely suppressed growth hormone secretion. J Clin Endocrinol Metab 96(1):E181–E188. https://doi.org/10.1210/jc.2010-1369
Mason WT, Rawlings SR (1988) Whole-cell recordings of ionic currents in bovine somatotrophs and their involvement in growth hormone secretion. J Physiol 405:577–593
McCusker RH, Wangsness PJ, Griel LC Jr, Kavanaugh JF (1985) Effects of feeding, fasting and refeeding on growth hormone and insulin in obese pigs. Physiol Behav 35(3):383–388
McDonald JK, Lumpkin MD, Samson WK, McCann SM (1985) Neuropeptide Y affects secretion of luteinizing hormone and growth hormone in ovariectomized rats. Proc Natl Acad Sci USA 82(2):561–564
Mollard P, Theler JM, Guerineau N, Vacher P, Chiavaroli C, Schlegel W (1994) Cytosolic Ca2+ of excitable pituitary cells at resting potentials is controlled by steady state Ca2+ currents sensitive to dihydropyridines. J Biol Chem 269(40):25158–25164
Nass R, Farhy LS, Liu J, Prudom CE, Johnson ML, Veldhuis P, Pezzoli SS, Oliveri MC, Gaylinn BD, Geysen HM, Thorner MO (2008) Evidence for acyl-ghrelin modulation of growth hormone release in the fed state. J Clin Endocrinol Metab 93(5):1988–1994. https://doi.org/10.1210/jc.2007-2234
Norrelund H (2005) The metabolic role of growth hormone in humans with particular reference to fasting. Growth Hormon IGF Res 15(2):95–122. https://doi.org/10.1016/j.ghir.2005.02.005
Norrelund H, Nair KS, Jorgensen JO, Christiansen JS, Moller N (2001) The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown. Diabetes 50(1):96–104
Norrelund H, Nair KS, Nielsen S, Frystyk J, Ivarsen P, Jorgensen JO, Christiansen JS, Moller N (2003) The decisive role of free fatty acids for protein conservation during fasting in humans with and without growth hormone. J Clin Endocrinol Metab 88(9):4371–4378. https://doi.org/10.1210/jc.2003-030267
Obal F Jr, Krueger JM (2004) GHRH and sleep. Sleep Med Rev 8(5):367–377. https://doi.org/10.1016/j.smrv.2004.03.005
Oerter KE, Guardabasso V, Rodbard D (1986) Detection and characterization of peaks and estimation of instantaneous secretory rate for episodic pulsatile hormone secretion. Comput Biomed Res 19(2):170–191
Osterstock G, Mitutsova V, Barre A, Granier M, Fontanaud P, Chazalon M, Carmignac D, Robinson IC, Low MJ, Plesnila N, Hodson DJ, Mollard P, Mery PF (2016) Somatostatin triggers rhythmic electrical firing in hypothalamic GHRH neurons. Sci Rep 6:24394. https://doi.org/10.1038/srep24394
Peacey SR, Toogood AA, Veldhuis JD, Thorner MO, Shalet SM (2001) The relationship between 24-hour growth hormone secretion and insulin-like growth factor I in patients with successfully treated acromegaly: impact of surgery or radiotherapy. J Clin Endocrinol Metab 86(1):259–266. https://doi.org/10.1210/jcem.86.1.7154
Pecile A, Muller EE, Felici M, Netti C, Cocchi D (1971) Influence of insulin injected into the lateral ventricle on pituitary growth-hormone release in the rat. J Endocrinol 50(1):51–58
Pietrowsky R, Meyrer R, Kern W, Born J, Fehm HL (1994) Effects of diurnal sleep on secretion of cortisol, luteinizing hormone, and growth hormone in man. J Clin Endocrinol Metab 78(3):683–687. https://doi.org/10.1210/jcem.78.3.8126142
Plotsky PM, Vale W (1985) Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophysial-portal circulation of the rat. Science 230(4724):461–463
Proudan N, Peroski M, Grignol G, Merchenthaler I, Dudas B (2015) Juxtapositions between the somatostatinergic and growth hormone-releasing hormone (GHRH) neurons in the human hypothalamus. Neuroscience 297:205–210. https://doi.org/10.1016/j.neuroscience.2015.03.054
Raben MS (1959) Human growth hormone. Diabetes 8(3):232–233
Riedel M, Hoeft B, Blum WF, von zur Muhlen A, Brabant G (1995) Pulsatile growth hormone secretion in normal-weight and obese men: differential metabolic regulation during energy restriction. Metabolism 44(5):605–610
Roh SG, Nie GY, Loneragan K, Gertler A, Chen C (2001) Direct modification of somatotrope function by long-term leptin treatment of primary cultured ovine pituitary cells. Endocrinology 142(12):5167–5171. https://doi.org/10.1210/endo.142.12.8559
Romero MI, Phelps CJ (1997) Identification of growth hormone-releasing hormone and somatostatin neurons projecting to the median eminence in normal and growth hormone-deficient Ames dwarf mice. Neuroendocrinology 65(2):107–116
Rose SR, Municchi G (1999) Six-hour and four-hour nocturnal sampling for growth hormone. J Pediatr Endocrinol Metab 12(2):167–173
Sainsbury A, Schwarzer C, Couzens M, Fetissov S, Furtinger S, Jenkins A, Cox HM, Sperk G, Hokfelt T, Herzog H (2002) Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice. Proc Natl Acad Sci USA 99(13):8938–8943. https://doi.org/10.1073/pnas.132043299
Sanchez F, Adriaenssens T, Romero S, Smitz J (2010) Different follicle-stimulating hormone exposure regimens during antral follicle growth alter gene expression in the cumulus-oocyte complex in mice. Biol Reprod 83(4):514–524. https://doi.org/10.1095/biolreprod.109.083311
Santen RJ, Bardin CW (1973) Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanisms. J Clin Invest 52(10):2617–2628. https://doi.org/10.1172/JCI107454
Sartor O, Bowers CY, Chang D (1985) Parallel studies of His-DTrp-Ala-Trp-DPhe-Lys-NH2 and human pancreatic growth hormone-releasing factor-44-NH2 in rat primary pituitary cell monolayer culture. Endocrinology 116(3):952–957. https://doi.org/10.1210/endo-116-3-952
Schaefer F (1996) Pathogenic mechanisms underlying the variable response to recombinant human growth hormone in children with chronic renal failure. Br J Clin Pract Suppl 85:23–25
Schindler WJ, Hutchins MO, Septimus EJ (1972) Growth hormone secretion and control in the mouse. Endocrinology 91(2):483–490. https://doi.org/10.1210/endo-91-2-483
Schlegel W, Winiger BP, Mollard P, Vacher P, Wuarin F, Zahnd GR, Wollheim CB, Dufy B (1987) Oscillations of cytosolic Ca2+ in pituitary cells due to action potentials. Nature 329(6141):719–721. https://doi.org/10.1038/329719a0
Shah N, Evans WS, Veldhuis JD (1999) Actions of estrogen on pulsatile, nyctohemeral, and entropic modes of growth hormone secretion. Am J Phys 276(5 Pt 2):R1351–R1358
Shiotani Y, Sakagami M, Fujimoto K, Ban T (1971) Influence of hypothalamic stimulation upon the ultrastructure of the anterior pituitary gland. Part 1. Somatotrophs. Med J Osaka Univ 21(4):215–229
Sinha Y, Lewis UJ, Vanderlaan WP (1972) Effects of administering antisera to mouse growth hormone and prolactin on gain in litter weight and on mammary nucleic acid content of lactating C3H mice. J Endocrinol 55(1):31–40
Steyn FJ, Huang L, Ngo ST, Leong JW, Tan HY, Xie TY, Parlow AF, Veldhuis JD, Waters MJ, Chen C (2011) Development of a method for the determination of pulsatile growth hormone secretion in mice. Endocrinology 152(8):3165–3171. https://doi.org/10.1210/en.2011-0253
Steyn FJ, Xie TY, Huang L, Ngo ST, Veldhuis JD, Waters MJ, Chen C (2013) Increased adiposity and insulin correlates with the progressive suppression of pulsatile GH secretion during weight gain. J Endocrinol 218(2):233–244. https://doi.org/10.1530/JOE-13-0084
Steyn FJ, Tolle V, Chen C, Epelbaum J (2016) Neuroendocrine regulation of growth hormone secretion. Compr Physiol 6(2):687–735. https://doi.org/10.1002/cphy.c150002
Stojilkovic SS, Tabak J, Bertram R (2010) Ion channels and signaling in the pituitary gland. Endocr Rev 31(6):845–915. https://doi.org/10.1210/er.2010-0005
Surya S, Horowitz JF, Goldenberg N, Sakharova A, Harber M, Cornford AS, Symons K, Barkan AL (2009) The pattern of growth hormone delivery to peripheral tissues determines insulin-like growth factor-1 and lipolytic responses in obese subjects. J Clin Endocrinol Metab 94(8):2828–2834. https://doi.org/10.1210/jc.2009-0638
Tan HY, Steyn FJ, Huang L, Cowley M, Veldhuis JD, Chen C (2016) Hyperphagia in male melanocortin 4 receptor deficient mice promotes growth independently of growth hormone. J Physiol 594(24):7309–7326. https://doi.org/10.1113/JP272770
Tannenbaum GS, Martin JB, Colle E (1976) Ultradian growth hormone rhythm in the rat: effects of feeding, hyperglycemia, and insulin-induced hypoglycemia. Endocrinology 99(3):720–727. https://doi.org/10.1210/endo-99-3-720
Tannenbaum GS, Rorstad O, Brazeau P (1979) Effects of prolonged food deprivation on the ultradian growth hormone rhythm and immunoreactive somatostatin tissue levels in the rat. Endocrinology 104(6):1733–1738. https://doi.org/10.1210/endo-104-6-1733
Tsaneva-Atanasova K, Sherman A, van Goor F, Stojilkovic SS (2007) Mechanism of spontaneous and receptor-controlled electrical activity in pituitary somatotrophs: experiments and theory. J Neurophysiol 98(1):131–144. https://doi.org/10.1152/jn.00872.2006
Umpleby AM, Russell-Jones DL (1996) The hormonal control of protein metabolism. Bailliere Clin Endocrinol Metab 10(4):551–570
Urban RJ, Evans WS, Rogol AD, Kaiser DL, Johnson ML, Veldhuis JD (1988) Contemporary aspects of discrete peak-detection algorithms. I. The paradigm of the luteinizing hormone pulse signal in men. Endocr Rev 9(1):3–37. https://doi.org/10.1210/edrv-9-1-3
Vahl N, Moller N, Lauritzen T, Christiansen JS, Jorgensen JO (1997) Metabolic effects and pharmacokinetics of a growth hormone pulse in healthy adults: relation to age, sex, and body composition. J Clin Endocrinol Metab 82(11):3612–3618. https://doi.org/10.1210/jcem.82.11.4388
Van Cauter E (1988) Estimating false-positive and false-negative errors in analyses of hormonal pulsatility. Am J Phys 254(6 Pt 1):E786–E794
Van den Berghe G (1999) Growth hormone secretagogues in critical illness. Horm Res 51(Suppl 3):21–28. https://doi.org/10.1159/000053158
Van Goor F, Zivadinovic D, Martinez-Fuentes AJ, Stojilkovic SS (2001) Dependence of pituitary hormone secretion on the pattern of spontaneous voltage-gated calcium influx. Cell type-specific action potential secretion coupling. J Biol Chem 276(36):33840–33846. https://doi.org/10.1074/jbc.M105386200
Vandenberg BF, Rossen JD, Grover-McKay M, Shammas NW, Burns TL, Rezai K (1996) Evaluation of diabetic patients for renal and pancreas transplantation: noninvasive screening for coronary artery disease using radionuclide methods. Transplantation 62(9):1230–1235
Veldhuis JD, Johnson ML (1986) Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Phys 250(4 Pt 1):E486–E493
Veldhuis JD, Iranmanesh A, Ho KK, Waters MJ, Johnson ML, Lizarralde G (1991) Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. J Clin Endocrinol Metab 72(1):51–59. https://doi.org/10.1210/jcem-72-1-51
Veldhuis JD, Roemmich JN, Rogol AD (2000) Gender and sexual maturation-dependent contrasts in the neuroregulation of growth hormone secretion in prepubertal and late adolescent males and females—a general clinical research center-based study. J Clin Endocrinol Metab 85(7):2385–2394. https://doi.org/10.1210/jcem.85.7.6697
Veldhuis JD, Roemmich JN, Richmond EJ, Bowers CY (2006) Somatotropic and gonadotropic axes linkages in infancy, childhood, and the puberty-adult transition. Endocr Rev 27(2):101–140. https://doi.org/10.1210/er.2005-0006
Veldhuis JD, Keenan DM, Pincus SM (2008) Motivations and methods for analyzing pulsatile hormone secretion. Endocr Rev 29(7):823–864. https://doi.org/10.1210/er.2008-0005
Watanobe H, Habu S (2002) Leptin regulates growth hormone-releasing factor, somatostatin, and alpha-melanocyte-stimulating hormone but not neuropeptide Y release in rat hypothalamus in vivo: relation with growth hormone secretion. J Neurosci 22(14):6265–6271. https://doi.org/10.1523/JNEUROSCI.22-14-06265.2002
Watts G (2007) Nobel prize is awarded for work leading to “knockout mouse”. BMJ 335(7623):740. https://doi.org/10.1136/bmj.39364.367361.DB
Weltman JY, Veldhuis JD, Weltman A, Kerrigan JR, Evans WS, Rogol AD (1990) Reliability of estimates of pulsatile characteristics of luteinizing hormone and growth hormone release in women. J Clin Endocrinol Metab 71(6):1646–1652. https://doi.org/10.1210/jcem-71-6-1646
Williams T, Berelowitz M, Joffe SN, Thorner MO, Rivier J, Vale W, Frohman LA (1984) Impaired growth hormone responses to growth hormone-releasing factor in obesity. A pituitary defect reversed with weight reduction. N Engl J Med 311(22):1403–1407. https://doi.org/10.1056/NEJM198411293112203
Winer LM, Shaw MA, Baumann G (1990) Basal plasma growth hormone levels in man: new evidence for rhythmicity of growth hormone secretion. J Clin Endocrinol Metab 70(6):1678–1686. https://doi.org/10.1210/jcem-70-6-1678
Xu J, Zhang Y, Berry PA, Jiang J, Lobie PE, Langenheim JF, Chen WY, Frank SJ (2011) Growth hormone signaling in human T47D breast cancer cells: potential role for a growth hormone receptor-prolactin receptor complex. Mol Endocrinol 25(4):597–610. https://doi.org/10.1210/me.2010-0255
Yamazaki M, Kobayashi H, Tanaka T, Kangawa K, Inoue K, Sakai T (2004) Ghrelin-induced growth hormone release from isolated rat anterior pituitary cells depends on intracellullar and extracellular Ca2+ sources. J Neuroendocrinol 16(10):825–831. https://doi.org/10.1111/j.1365-2826.2004.01237.x
Yang SK, Parkington HC, Blake AD, Keating DJ, Chen C (2005) Somatostatin increases voltage-gated K+ currents in GH3 cells through activation of multiple somatostatin receptors. Endocrinology 146(11):4975–4984. https://doi.org/10.1210/en.2005-0696
Yang SK, Parkington HC, Epelbaum J, Keating DJ, Chen C (2007) Somatostatin decreases voltage-gated Ca2+ currents in GH3 cells through activation of somatostatin receptor 2. Am J Physiol Endocrinol Metab 292(6):E1863–E1870. https://doi.org/10.1152/ajpendo.00047.2007
Yang SK, Wang K, Parkington H, Chen C (2008) Involvement of tetrodotoxin-resistant Na+ current and protein kinase C in the action of growth hormone (GH)-releasing hormone on primary cultured somatotropes from GH-green fluorescent protein transgenic mice. Endocrinology 149(9):4726–4735. https://doi.org/10.1210/en.2008-0405
Yang SK, Steyn F, Chen C (2012) Influence of membrane ion channel in pituitary somatotrophs by hypothalamic regulators. Cell Calcium 51(3–4):231–239. https://doi.org/10.1016/j.ceca.2011.12.005
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Key References: See Main List for Reference Details
Key References: See Main List for Reference Details
-
Huang et al. (2014). This article demonstrated inhibitory effect of NPY on GH secretion via NPY receptors.
-
Steyn et al. (2011). This article reported an establishment of GH pulsatile analysis method in conscious free-moving mouse.
-
Steyn et al. (2016). An important summary of feedback regulations of GH.
-
Stojilkovic et al. (2010). An important summary of ion channels and signaling system in anterior pituitary gland.
-
Umpleby and Russell-Jones (1996). This article reports the function of pulsatile GH in regulating protein metabolism.
-
Veldhuis et al. (2008). This review details the deconvolution analysis in analyzing pulsatile hormone profiles.
-
Yang et al. (2012). An important summary of membrane ion channels in the regulation of GH secretion.
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Huang, L., Chen, Y., Huang, Z., Chen, C. (2020). Neuroendocrine and Metabolic Regulation of Plasma Growth Hormone Secretory Profiles. In: Lemos, J., Dayanithi, G. (eds) Neurosecretion: Secretory Mechanisms. Masterclass in Neuroendocrinology, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-030-22989-4_10
Download citation
DOI: https://doi.org/10.1007/978-3-030-22989-4_10
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-22988-7
Online ISBN: 978-3-030-22989-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)