60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-GH axis: the past 60 years

    1. P E Clayton1,2
    1. 1Centre for Paediatrics and Child Health, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UK
      2Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UK
      3Department of Endocrinology, The Christie Hospital NHS Foundation Trust, Manchester, M20 4BX, UK
      4Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, M13 9WL, UK
    1. Correspondence should be addressed to P E Clayton; Email: peter.clayton{at}manchester.ac.uk


    At the time of the publication of Geoffrey Harris's monograph on ‘Neural control of the pituitary gland’ 60 years ago, the pituitary was recognised to produce a growth factor, and extracts administered to children with hypopituitarism could accelerate growth. Since then our understanding of the neuroendocrinology of the GH axis has included identification of the key central components of the GH axis: GH-releasing hormone and somatostatin (SST) in the 1970s and 1980s and ghrelin in the 1990s. Characterisation of the physiological control of the axis was significantly advanced by frequent blood sampling studies in the 1980s and 1990s; the pulsatile pattern of GH secretion and the factors that influenced the frequency and amplitude of the pulses have been defined. Over the same time, spontaneously occurring and targeted mutations in the GH axis in rodents combined with the recognition of genetic causes of familial hypopituitarism demonstrated the key factors controlling pituitary development. As the understanding of the control of GH secretion advanced, developments of treatments for GH axis disorders have evolved. Administration of pituitary-derived human GH was followed by the introduction of recombinant human GH in the 1980s, and, more recently, by long-acting GH preparations. For GH excess disorders, dopamine agonists were used first followed by SST analogues, and in 2005 the GH receptor blocker pegvisomant was introduced. This review will cover the evolution of these discoveries and build a picture of our current understanding of the hypothalamo-GH axis.

    • Received in final form 26 May 2015
    • Accepted 3 June 2015
    • Made available online as an Accepted Preprint 3 June 2015
    | Table of Contents