Endocrine Abstracts

The neuroendocrine cascade regulating episodic growth hormone (GH) secretion plays a central role in post-natal growth and metabolism. Intermingling of GH cells with other pituitary cell types and the complex distribution of the hypothalamic GHRH neurons makes both the cell types difficult targets for selective physical or chemical manipulation. On the other hand, they are excellent targets for physiological transgenesis since their major secretory products derive from highly expressed well-characterised genes whose promoters provide unique cell specificity. A wide range of transgene products can target different subcellular mechanisms involved in hormone synthesis, transport, storage and secretion, as well as the proliferation and elimination of the cells themselves. Combining these transgenic manipulations with in vivo analysis provides novel opportunities for studying integrative physiological processes during post-natal development and for generating new animal models of human endocrine pathophysiology. Whilst the molecular interventions are specific, the phenotypic consequences are often surprising, sometimes informative and occasionally useful. I will describe some of our recent attempts to combine physiology and transgenesis in the hypothalamo/pituitary GHRH/GH axis, ranging in focus from molecular and subcellular events in single cells, through multicellular organization and coordinated functions in endocrine cell populations, up to communication and feedback between different components of the neuroendocrine cascade and its target tissues. By learning how these interact to generate an integrated response to internal and external cues we hope to gain a better understanding of the physiological mechanisms regulating the GH axis in health and disease