The hypothalamo-growth hormone axis: the past 60 years.

Abstract

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 growth hormone (GH) axis has included identification of the key central components of the GH axis - GHRH and somatostatin in the 1970's and 80's - and in the 1990's ghrelin. Characterisation of the physiological control of the axis was significantly advanced by frequent blood sampling studies in the 1980's and 90's; the pulsatile pattern of GH secretion and the factors that influenced the frequency and amplitude of the pulses has 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 understanding of the control of growth hormone secretion advanced, so developments of treatments for GH axis disorders have evolved. Administration of pituitary derived human growth hormone was followed by the introduction of recombinant human growth hormone in the 1980's, and more recently long-acting GH preparations. For growth hormone excess disorders, firstly dopamine agonists were used followed by somatostatin analogues and in 2005 the introduction of the GH receptor blocker pegvisomant. This review will cover the evolution of these discoveries, and build a picture of our current understanding the hypothalamo-growth hormone axis.