The molecular basis of growth hormone deficiency

A well-known law states that 'if a thing can go wrong it will go wrong'. This clearly applies to the hypothalamic-pituitary-somatic axis as to many other physiological and biochemical systems. Defects of this axis, giving rise to stunted growth, can occur at several different points, as has been discussed in detail in this review. Defects at the level of the brain can lead to inadequate production or secretion of the factors that control growth hormone secretion. Defects at the level of the pituitary can lead to failure to produce or secrete adequate quantities of growth hormone, or to production of inactive hormone. Defects at the level of target organs can lead to inability to respond to growth hormone or somatomedins. The axis involved in the production and effects of growth hormone is a complex one, and defects have been identified at most of the points that 'could go wrong', although in many cases the molecular details are far from fully understood. Increased understanding of the biochemistry and physiology of the hormonal control of growth, and of the impairments to which it is subject, should provide an improved basis for treatment of growth defects. Nevertheless, there remain many points at which our knowledge is very incomplete. The field is a rapidly moving one and further developments in both basic understanding and clinical treatment are to be expected during the next few years.