Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-8448b6f56d-c47g7 Total loading time: 0 Render date: 2024-04-23T14:41:46.399Z Has data issue: false hasContentIssue false

6 - Neurotransmitter and neuropeptide control of hypothalamic, pituitary and other hormones

Published online by Cambridge University Press:  05 June 2015

Michael Wilkinson  and
Richard E. Brown
Michael Wilkinson
Affiliation:
Dalhousie University, Nova Scotia
Richard E. Brown
Affiliation:
Dalhousie University, Nova Scotia
Get access

Summary

Previous chapters have discussed the endocrine glands and their hormones (Chapter 2), the hormones of the pituitary gland (Chapter 3), the hypothalamic hormones (Chapter 4) and neurotransmitters (Chapter 5). This chapter will describe how neurotransmitters influence the release of hypothalamic and pituitary hormones and the hormones of the adrenal medulla, pancreas, thymus and gastrointestinal tract. It will also examine the electrophy-siological properties of neurosecretory cells and the effects of drugs on the release of neurohormones.

The cascade of chemical messengers

As shown in Figure 6.1, and using the adrenal gland as an example, there is a cascade of chemical messengers that regulate target tissue function from the brain to the endocrine glands. For example, neurons release a neurotransmitter that regulates the secretion of neurohormones (such as CRH) from hypothalamic neurosecretory cells. These hypothalamic hormones stimulate the cells of the adenohypophysis (anterior pituitary) to synthesize and release their hormones. Many pituitary hormones, such as ACTH, act on endocrine target cells, such as the adrenal cortex, causing them to synthesize and release their own hormones (e.g. cortisol) which then stimulate biochemical changes in target cells elsewhere in the body, including the brain. In each step of this pathway, the individual neurotransmitters and peptide hormones bind to membrane receptors that activate a second messenger, such as cAMP, within the target cell (see Chapter 10). Steroid hormones (such as cortisol) act on receptors located inside the target cells (see Chapter 9). This chapter describes the effects of neurotransmitters on hypothalamic neurosecretory cells.

Neural control of hypothalamic neurosecretory cells

6.2.1 Neural input to the endocrine hypothalamus

Figure 4.1 illustrates the different nuclei of the hypothalamus, many of which have neurons, or nerve terminals, which release a variety of neurotransmitters including GABA, glutamate, kisspeptin, opioids, dopamine, norepinephrine and serotonin. These neurotransmitters all bind to receptors on hypothalamic neurosecretory cells. This chapter describes the magnocellular hypothalamic neurosecretory cells of the paraventricular and supraoptic nuclei (PVN and SON), whose axons terminate in the posterior pituitary, and the parvicellular hypothalamic neurosecretory cells, whose axons terminate in the median eminence (see Figure 3.1).

Type
Chapter
Information
An Introduction to Neuroendocrinology , pp. 120 - 156
Publisher: Cambridge University Press
Print publication year: 2015

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aguzzi, A., Barres, B. A. and Bennett, M. L. (2013). “Microglia: scapegoat, saboteur, or something else?”Science 339, 156–161.CrossRefGoogle ScholarPubMed
Ahren, B. (1986). “Thyroid neuroendocrinology: neural regulation of thyroid hormone secretion,” Endocr Rev 7, 149–155.CrossRefGoogle ScholarPubMed
Aguilar, E., Tena-Sempere, M. and Pinilla, L. (2005). “Role of excitatory amino acids in the control of growth hormone secretion,” Endocrinology 28, 295–302.Google ScholarPubMed
Allen, N. J. and Barres, B. A. (2009). “Glia – more than just brain glue,” Nature 457, 675–677.CrossRefGoogle ScholarPubMed
Bealer, S. L., Armstrong, W. E. and Crowley, W. R. (2010). “Oxytocin release in magnocellular nuclei: neurochemical mediators and functional significance during gestation,” Am J Physiol Regul Integr Comp Physiol 299, R452–458.CrossRefGoogle ScholarPubMed
Berne, R. M. and Levy, M. N. (2000). Principles of Physiology, rd edn. (St. Louis, MO: Mosby).Google Scholar
Boyda, H. N., Tse, L., Procyshyn, R. M., Honer, W. G. and Barr, A. M. (2010). “Preclinical models of antipsychotic drug-induced metabolic side effects,” Trends Pharmacol Sci 31, 484–497.CrossRefGoogle ScholarPubMed
Busnardo, C., Crestani, C. C., Resstel, L. B., Tavares, R. F., Antunes-Rodrigues, J. and Correa, F. M. (2012). “Ionotropic glutamate receptors in hypothalamic paraventricular and supraoptic nuclei mediate vasopressin and oxytocin release in unanesthetized rats,” Endocrinology 153, 2323–2331.CrossRefGoogle ScholarPubMed
Carrasco, G. A. and Van de Kar, L. D. (2003). “Neuroendocrine pharmacology of stress,” Eur J Pharmacol 463, 235–272.CrossRefGoogle ScholarPubMed
Catania, A., Airaghi, L., Colombo, G. and Lipton, J. M. (2000). “Alpha-melanocyte-stimulating hormone in normal human physiology and disease states,” Trends Endocrinol Metab 11, 304–308.CrossRefGoogle ScholarPubMed
Chan, Y. M., Broder-Fingert, S. and Seminara, S. B. (2009). “Reproductive functions of kisspeptin and GPR54 across the life cycle of mice and men,” Peptides 30, 42–48.CrossRefGoogle ScholarPubMed
Chapman, D. B., Theodosis, D. T., Montagnese, C., Poulain, D. A. and Morris, J. F. (1986). “Osmotic stimulation causes structural plasticity of neurone-glia relationships of the oxytocin but not vasopressin secreting neurones in the hypothalamic supraoptic nucleus,” Neuroscience 17, 679–686.CrossRefGoogle Scholar
Clarke, I. J. and Parkington, H. C. (2013). “Gonadotropin inhibitory hormone (GnIH) as a regulator of gonadotropes,” Mol Cell Endocr 385, 36–44.Google ScholarPubMed
Clasadonte, J., Poulain, P., Hanchate, N. K., Corfas, G., Ojeda, S. R. and Prevot, V. (2011). “Prostaglandin E2 release from astrocytes triggers gonadotropin releasing hormone (GnRH) neuron firing via EP2 receptor activation,” Proc Natl Acad Sci USA 108, 16104–16109.CrossRefGoogle ScholarPubMed
D'Albora, H., Anesetti, G., Lombide, P., Dees, W. L. and Ojeda, S. R. (2002). “Intrinsic neurons in the mammalian ovary,” Microsc Res Tech 59, 484–489.CrossRefGoogle ScholarPubMed
Egli, M., Leeners, B. and Kruger, T. H. (2010). “Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction,” Reprod 140, 643–654.CrossRefGoogle ScholarPubMed
Fekete, C. and Lechan, R. M. (2013). “Central regulation of the hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions,” Endocr Revs 35, 159–194.Google ScholarPubMed
Fisher, J. A. and Ronald, L. M. (2010). “Sex, gender, and pharmaceutical politics: from drug development to marketing,” Gend Med 7, 357–370.CrossRefGoogle ScholarPubMed
Freeman, M. E., Kanyicska, B., Lerant, A. and Nagy, G. (2000). “Prolactin: structure, function, and regulation of secretion,”Physiol Rev 80, 1523–1631.CrossRefGoogle Scholar
Gan, E. H. and Quinton, R. (2010). “Physiological significance of the rhythmic secretion of hypothalamic and pituitary hormones,” Prog Brain Res 181, 111–126.Google ScholarPubMed
Gerendai, I., Banczerowski, P. and Halasz, B. (2005). “Functional significance of the innervation of the gonads,” Endocrine 28, 309–318.CrossRefGoogle ScholarPubMed
Graeber, M. B. (2010). “Changing face of microglia,” Science 330, 783–788.CrossRefGoogle ScholarPubMed
Halassa, M. M. and Haydon, P. G. (2010). “Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior,” Ann Rev Physiol 72, 335–355.CrossRefGoogle ScholarPubMed
Haydon, P. G. (2001). “Glia: listening and talking to the synapse,” Nat Rev Neurosci 2, 185–193.CrossRefGoogle ScholarPubMed
Herbison, A. E. (1997). “Noradrenergic regulation of cyclic GnRH secretion,” Revs Reprod 2, 1–6.Google ScholarPubMed
Horowski, R. and Graf, K. J. (1979). “Neuroendocrine effects of neuropsychotropic drugs and their possible influence on toxic reactions in animals and man – the role of the dopamine-prolactin system,” Arch Toxicol(Suppl. 2), 93–104.Google Scholar
Iversen, L. L., Iversen, S. D., Bloom, F. E. and Roth, R. H. (2009). Introduction to Neuropsychopharmacology (New York: Oxford University Press).CrossRefGoogle Scholar
Jackson, I. M. (1998). “The thyroid axis and depression,” Thyroid 8, 951–956.CrossRefGoogle ScholarPubMed
Jayasena, C. N. and Dhillo, W. S. (2009). “Kisspeptin offers a novel therapeutic target in reproduction,” Curr Opin Investig Drugs 10, 311–318.Google ScholarPubMed
Kenna, H. A., Jiang, B. and Rasgon, N. L. (2009). “Reproductive and metabolic abnormalities associated with bipolar disorder and its treatment,” Harv Rev Psychiatry 17, 138–146.CrossRefGoogle ScholarPubMed
Keverne, E. B. (2005). “Odor here, odor there: chemosensation and reproductive function,” Nat Neurosci 8, 1637–1638.CrossRefGoogle ScholarPubMed
Khoo, B. and Grossman, A. B. (2007). “Normal and abnormal physiology of the hypothalamus and anterior pituitary” in Neuroendocrinology, Hypothalamus, and Pituitary, www.endotext.org/neuroendo/index.htm.
Kiba, T. (2004). “Relationships between the autonomic nervous system and the pancreas including regulation of regeneration and apoptosis: recent developments,” Pancreas 29, e51–58.CrossRefGoogle ScholarPubMed
de Kloet, E. R., Joels, M. and Holsboer, F. (2005). “Stress and the brain: from adaptation to disease,” Nat Rev Neurosci 6, 463–475.CrossRefGoogle ScholarPubMed
Krsmanovic, L. Z., Hu, L., Leung, P. K., Feng, H. and Catt, K. J. (2009). “The hypothalamic GnRH pulse generator: multiple regulatory mechanisms,” Trends Endocrinol Metab 20, 402–408.CrossRefGoogle ScholarPubMed
Krystal, J. H., D'Souza, D. C., Karper, L. P., Bennett, A., Abi-Dargham, A., Abi-Saab, D.et al. (1999). “Interactive effects of subanesthetic ketamine and haloperidol in healthy humans,” Psychopharmacology (Berl) 145, 193–204.CrossRefGoogle ScholarPubMed
Lightman, S. L. and Conway-Campbell, B. L. (2010). “The crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration,” Nat Rev Neurosci 11, 710–718.CrossRefGoogle ScholarPubMed
Lim, C. T., Kola, B., Korbonits, M. and Grossman, A. B. (2010). “Ghrelin's role as a major regulator of appetite and its other functions in neuroendocrinology,” Prog Brain Res 182, 189–205.Google ScholarPubMed
Majdoubi, M. E., Poulain, D. A. and Theodosis, D. T. (1996). “The glutamatergic innervation of oxytocin- and vasopressin-secreting neurons in the rat supraoptic nucleus and its contribution to lactation-induced synaptic plasticity,” Europ J Neurosci 8, 1377–1389.CrossRefGoogle ScholarPubMed
Manson, J. E. (2010). “Pain: sex differences and implications for treatment,” Metabolism 59(Suppl. 1), S16–S20.CrossRefGoogle ScholarPubMed
Mariotti, S. (2011). “Physiology of the hypothalamic-pituitary thyroidal system” in Grossman, A. B. (ed.), Neuroendocrinology, Hypothalamus, and Pituitary, Endotext.org, www.thyroidmanager.org/chapter/physiology-of-the-hypothalmic-pituitary-thyroidal-system/.
Martin, D. L. (1992). “Synthesis and release of neuroactive substances by glial cells,” Glia 5, 81–94.CrossRefGoogle ScholarPubMed
Mayer, C. M., Fick, L. J., Gingerich, S. and Belsham, D. D. (2009). “Hypothalamic cell lines to investigate neuroendocrine control mechanisms,” Front Neuroendocr 30, 405–423.CrossRefGoogle ScholarPubMed
McCann, S. M. (1980). “Fifth Geoffrey Harris memorial lecture. Control of anterior pituitary hormone release by brain peptides,” Neuroendocrinology 31, 355–363.CrossRefGoogle Scholar
Nance, D. M. and Sanders, V. M. (2007). “Autonomic innervation and regulation of the immune system (1987–2007),” Brain Behav Immun 21, 736–745.CrossRefGoogle Scholar
Nedergaard, M., Ransom, B. and Goldman, S. A. (2003). “New roles for astrocytes: redefining the functional architecture of the brain,” Trends Neurosci 26, 523–530.CrossRefGoogle Scholar
Nicholls, J. G., Martin, A. R., Fuchs, P. A., Brown, D. A., Diamond, M. E. and Weisblat, D. (2011). From Neuron to Brain, th edn. (Sunderland, MA: Sinauer).Google Scholar
Nillni, E. A. (2010). “Regulation of the hypothalamic thyrotropin releasing hormone (TRH) neuron by neuronal and peripheral inputs,” Front Neuroendocr 31, 134–156.CrossRefGoogle ScholarPubMed
Nishihara, M., Takeuchi, Y., Tanaka, T. and Mori, Y. (1999). “Electrophysiological correlates of pulsatile and surge gonadotrophin secretion,” Rev Reprod 4, 110–116.CrossRefGoogle ScholarPubMed
Oakley, A. E., Clifton, D. K. and Steiner, R. A. (2009). “Kisspeptin signaling in the brain,” Endocr Rev 30, 713–743.CrossRefGoogle Scholar
Ojeda, S. R. and Negro-Vilar, A. (1985). “Prostaglandin E2-induced luteinizing hormone releasing hormone release involves mobilization of intracellular Ca2+,” Endocrinology 116, 1763–1770.CrossRefGoogle Scholar
Ojeda, S. R., Lomniczi, A. and Sandau, U. S. (2008). “Glial-gonadotrophin hormone (GnRH) neurone interactions in the median eminence and the control of GnRH secretion,” J Neuroendocr 20, 732–742.CrossRefGoogle ScholarPubMed
Okamura, H., Murata, K., Sakamoto, K., Wakabayashi, Y., Ohkura, S., Takeuchi, Y.et al. (2010). “Male effect pheromone tickles the gonadotrophin-releasing hormone pulse generator,”J Neuroendocr 22, 825–832.CrossRefGoogle Scholar
O'Keane, V. (2008). “Antipsychotic-induced hyperprolactinaemia, hypogonadism and osteoporosis in the treatment of schizophrenia,” J Psychopharmacol 22, 70–75.CrossRefGoogle ScholarPubMed
Oliet, S. H. R., Panatier, A., Piet, R., Mothet, J.-P., Poulain, D. A. and Theodosis, D. T. (2008). “Neuron-glia interactions in the rat supraoptic nucleus,” Prog Brain Res 170, 109–117.Google ScholarPubMed
Onaka, T., Takayanagi, Y. and Leng, G. (2010). “Metabolic and stress-related roles of prolactin-releasing peptide,” Trends Endocrinol Metab 21, 287–293.CrossRefGoogle ScholarPubMed
Orio, F., Palomba, S., Colao, A., Tenuta, M., Dentico, C., Pettreta, M.et al. (2001). “Growth hormone secretion after baclofen administration in different phases of the menstrual cycle in healthy women,” Horm Res 55, 131–136.Google ScholarPubMed
Panatier, A. (2009). “Glial cells: indispensable partners of hypothalamic magnocellular neurones,” J Neuroendocr 21, 665–672.CrossRefGoogle ScholarPubMed
Perea, G., Navarette, M. and Araque, A. (2009). “Tripartite synapses: astrocytes process and control synaptic information,” Trends Neurosci 32, 421–431.CrossRefGoogle ScholarPubMed
Prevot, V., Bellefontaine, N., Baroncini, M., Sharif, A., Hanchate, N. K., Parkash, J.et al. (2010). “Gonadotrophin-releasing hormone nerve terminals, tanycytes and neurohaemal junction remodelling in the adult median eminence: functional consequences for reproduction and dynamic role of vascular endothelial cells,” J Neuroendocr 22, 639–649.Google ScholarPubMed
Purves, D., Augustine, G. J., Fitzpatrick, D., Hall, W. C., LaMantia, A.-S., McNamara, J. O.et al. (2008). Neuroscience, th edn. (Sunderland: Sinauer Associates).Google Scholar
Rainero, I., Valfrè, W., Savi, L., Gentile, S., Pinessi, L., Gianotti, L.et al. (2001). “Neuroendocrine effects of subcutaneous sumatriptan in patients with migraine,” J Endocrinol Invest 24, 310–314.CrossRefGoogle ScholarPubMed
Ramaswamy, S., Seminara, S. B., Ali, B., Ciofi, P., Amin, N. A. and Plant, T. M. (2010). “Neurokinin B stimulates GnRH release in the male monkey (Macaca mulatta) and is colocalized with kisspeptin in the arcuate nucleus,” Endocr 151, 4494–4503.CrossRefGoogle ScholarPubMed
Rettori, V., De Laurentiis, A. and Fernandez-Solari, J. (2010). “Alcohol and endocannabinoids: neuroendocrine interactions in the reproductive axis,” Exp Neurol 224, 15–22.CrossRefGoogle ScholarPubMed
Reynolds, G. P. and Kirk, S. L. (2010). “Metabolic side effects of antipsychotic drug treatment–pharmacological mechanisms,” Pharmacol Ther 125, 169–179.CrossRefGoogle ScholarPubMed
Roa, J., Aguilar, E., Dieguez, C., Pinilla, L. and Tena-Sempere, M. (2008). “New frontiers in kisspeptin/GPR54 physiology as fundamental gatekeepers of reproductive function,” Front Neuroendocr 29, 48–69.CrossRefGoogle ScholarPubMed
Saland, L. C. (2001). “The mammalian pituitary intermediate lobe: an update on innervation and regulation,” Brain Res Bull 54, 587–593.CrossRefGoogle ScholarPubMed
Sakuma, Y. (2002). “GnRH in the regulation of female rat sexual behavior,” Prog Brain Res 141, 293–301.Google ScholarPubMed
Schule, C. (2007). “Neuroendocrinological mechanisms of actions of antidepressant drugs,” J Neuroendocrinol 19, 213–226.CrossRefGoogle ScholarPubMed
Simonneaux, V. and Ribelayga, C. (2003). “Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters,” Pharmacol Rev 55, 325–395.CrossRefGoogle ScholarPubMed
Simpson, N., Maffei, A., Freeby, M., Borroughs, S., Freyberg, Z., Javitch, J.et al. (2012). “Dopamine-mediated autocrine inhibitory circuit regulating human insulin secretion in vitro,”Mol Endocr 26, 1757–1772.CrossRefGoogle Scholar
Sladek, C. D. and Kapoor, J. R. (2001). “Neurotransmitter/neuropeptide interactions in the regulation of neurohypophyseal hormone release,” Exp Neurol 171, 200–209.CrossRefGoogle ScholarPubMed
Sladek, C. D. and Song, Z. (2012). “Diverse roles of G-protein coupled receptors in the regulation of neurohypophyseal hormone secretion,” J Neuroendocr 24, 554–565.CrossRefGoogle ScholarPubMed
Smith, K. (2010). “Settling the great glia debate,” Nature 468, 160–162.CrossRefGoogle ScholarPubMed
Smith, M. J. and Jennes, L. (2001). “Neural signals that regulate GnRH neurones directly during the oestrous cycle,” Reprod 122, 1–10.CrossRefGoogle ScholarPubMed
Squire, L. R., Berg, D. E., Bloom, F. E., du Lac, S., Ghosh, A. and Spitzer, N. C. (2008). Fundamental Neuroscience, rd edn. (London: Academic Press).Google Scholar
Stern, P. (2010). “Glee for glia,” Science 330, 773.CrossRefGoogle ScholarPubMed
Stockhorst, U. (2005). “Classical conditioning of endocrine effects,” Curr Opin Psych 18, 181–187.CrossRefGoogle ScholarPubMed
Taylor, C., Fricker, A. D., Devi, L. A. and Gomes, I. (2005). “Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways,” Cell Signal 17, 549–557.CrossRefGoogle ScholarPubMed
Theodosis, D. T. (2002). “Oxytocin-secreting neurons: a physiological model of morphological neuronal and glial plasticity in the adult hypothalamus,” Front Neuroendocr 23, 101–135.CrossRefGoogle ScholarPubMed
Theodosis, D. T., Poulain, D. A. and Oliet, S. H. R. (2008). “Activity-dependent structural and functional plasticity of astrocyte-neuron interactions,” Physiol Rev 88, 983–1008.CrossRefGoogle ScholarPubMed
Tichomirowa, M. A., Keck, M. E., Schneider, H. J., Paez-Pereda, M., Renner, U., Holsboer, F.et al. (2005). “Endocrine disturbances in depression,” J Endocrinol Invest 28, 89–99.CrossRefGoogle ScholarPubMed
Ustione, A., Piston, D. W. and Harris, P. E. (2013). “Minireview: dopaminergic regulation of insulin secretion from the pancreatic islet,” Mol Endocr 27, 1198–1207.CrossRefGoogle ScholarPubMed
Valverde, I., Penalva, A. and Dieguez, C. (2000). “Influence of different serotonin receptor subtypes on growth hormone secretion,” Neuroendocrinology 71, 145–153.CrossRefGoogle ScholarPubMed
Van de Kar, L. D. and Blair, M. L. (1999). “Forebrain pathways mediating stress-induced hormone secretion,” Front Neuroendocr 20, 1–48.CrossRefGoogle ScholarPubMed
Van den Pol, A. N., Wuarin, J. P. and Dudek, F. E. (1990). “Glutamate, the dominant excitatory transmitter in neuroendocrine regulation,” Science 250, 1276–1278.CrossRefGoogle ScholarPubMed
Veldhuis, J. D., Keenan, D. M. and Pincus, S. M. (2010). “Regulation of complex pulsatile and rhythmic neuroendocrine systems: the male gonadal axis as a prototype,” Prog Brain Res 181, 79–110.Google ScholarPubMed
Vollenweider, F. X. and Kometer, M. (2010). “The neurobiology of psychedelic drugs: implications for the treatment of mood disorders,” Nat Rev Neurosci 11, 642–651.CrossRefGoogle ScholarPubMed
Volterra, A. and Meldolesi, J. (2005). “Astrocytes, from brain glue to communication elements: the revolution continues,” Nat Rev Neurosci 6, 626–640.CrossRefGoogle ScholarPubMed
Wake, H., Moorhouse, A. J. and Nabekura, J. (2011). “Functions of microglia in the central nervous system – beyond the immune response,” Neuron Glia Biol 7, 47–53.CrossRefGoogle ScholarPubMed
Wake, H., Moorhouse, A. J., Miyamoto, A. and Nabekura, J. (2012). “Microglia: actively surveying and shaping neuronal circuit structure and function,” Trends Neurosci 36, 209–217.Google ScholarPubMed
Wakerley, J. B. and Lincoln, D. W. (1973). “The milk-ejection reflex of the rat: a 20- to 40-fold acceleration in the firing of paraventricular neurones during oxytocin release,” J Endocrinol 57, 477–493.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×