Endocrine Abstracts

Pituitary hormones are released into the bloodstream in a pulsatile fashion in response to stimuli from their hypothalamic regulators. For efficient generation of hormone pulses, both the hypothalamic mechanisms and the pituitary target cells must exhibit a high degree of coordinated secretory activity. This is particularly important for the growth hormone (GH) axis since the target tissue responses are critically dependent on the temporal pattern of GH exposure, as well as the amount secreted. The pituitary cell populations also exhibit a high degree of plasticity, with both cell number and hormone reserves varying markedly in response to physiological needs. I shall describe some of our studies in which we are exploiting a variety of genetic approaches to image, manipulate or ablate single or multiple pituitary cell populations, both during development, or later in post-natal life. Studies of mice with disruption of genes involved in pituitary development have shed light on mechanisms underlying similar problems in children with pituitary deficits. We have targeted fluorescent proteins to cytoplasmic or secretory granule compartments in the GH and PRL (PRL) axes, which created models in which the distribution, and organization of these cell populations, their development and secretory activity can now be directly observed, both in vitro and in vivo. In other studies, expression of transgene products that alter receptor signaling, ion-transport or secretory vesicle packaging have enabled us to manipulate selectively, populations of these neuroendocrine cells, providing models of somatotroph loss that lead to more widespread compromise pituitary function. These approaches provide new tools to study pituitary endocrine cell function, not only at a single cell level, but more relevant to the organism, how they function as coordinated homotypic network of cells, and how changes in one population may alter proliferation and activity in other related cell networks.