Transgenes and physiology in the Growth Hormone axis: a view from the portal
Iain Robinson, London, UK
Neuroendocrine cascades regulate essential processes in integrative physiology, such as growth and metabolism, reproduction, and responses to stress. The pioneering work of Geoffrey Harris showed that the pituitary gland, the major endocrine regulator of these processes, is itself controlled by hypothalamic neurones that secrete their products into the hypophysial portal circulation. Intermingling of pituitary cell types and the complex anatomical distribution of the different hypothalamic neuronal systems makes them difficult targets for selective physical or chemical manipulation. However, their strong expression of major secretory products from genes with well characterised promoters makes them excellent targets for physiological transgenesis. We have been using a variety of transgenic approaches to image and manipulate different cellular processes in the hypothalamo/pituitary growth hormone (GH) axis and studying the consequences in vivo. The results have often been surprising, sometimes informative about the generation of GH pulses, and occasionally useful in elucidating mechanisms of pathology in animal models of human pituitary dysfunction. The adult pituitary gland is a dynamic structure that can adapt its cell populations, their 3D organisation, vascular flows and hormone outputs in response to changing physiological demands. Some of the mechanisms involved in normal pituitary development also contribute to its post-natal plasticity, not least via a population of stem/progenitor cells in the adult gland, which can give rise to new pituitary cells of all types. Integrative physiology has been characterised in the past as seeing how black boxes interact functionally in the context of the living organism. We are now beginning to look inside some of these boxes.