ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 S28.1

Plasticity in the growth hormone axis

Iain Robinson

MRC National Institute for Medical Research, London, UK.

Pituitary growth hormone (GH) is released in a highly pulsatile fashion in response to stimuli from its hypothalamic regulators, GH releasing hormone (GHRH) and somatostatin (SRIF), as well as feedback from peripheral signals. This interplay is complex, and still poorly understood. GHRH is a major factor in controlling pituitary GH synthesis and somatotroph cell number as well as GH secretion, and lack of GHRH or its receptor cause profound somatotroph hypoplasia and dwarfism. Whilst somatostatin can powerfully suppress GH release, chronic lack of SRIF has more subtle effects on GH secretory patterns, without a major effect on growth. Similarly, Ghrelin powerfully stimulates GH release, but the physiological relevance of endogenous Ghrelin for normal GH secretion remains unclear. For efficient generation of GH pulses, both the hypothalamic mechanisms and the pituitary target cells need to be highly coordinated in their secretory activity. This is important since the target tissue responses to GH depend on both the amount and the pattern of GH exposure. Recent imaging studies using transgenic mice with GH or GHRH cells tagged with GFP have shown that the pituitary cell populations are highly dynamic and show a remarkable degree of plasticity, with both cell number and hormone reserves varying in response to demands at different stages of life. Aging reduces the activity in the GH axis, but the mechanisms are not obviously related to failure or reduction in GHRH or GH cells, suggesting that the age related decrease in GH might be reversible. Analysis of other animal models in which hypothalamic or pituitary cells are disrupted in development or post-natally has shed light on mechanisms underlying similar problems in children with pituitary deficits. The cellular plasticity in the adult pituitary implies the presence of progenitor cells, and we have recently identified and grown such cells in culture, and shown that they can give rise to all the pituitary cell types. Such studies extend our understanding of normal and pathological pituitary plasticity underlying GH secretion, and enable us to test some novel potential therapeutic approaches.

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