Endocrine Abstracts

Changes in hormone output to regulate physiological processes is a feature of all endocrine systems, with the added complication that for many systems, the pattern as well as level of output, determines the response of target tissues. Periodic patterns of hormone secretion can occur over multiple time scales, from ultradian to circadian, infradian, and circannual and may be dependent on physiological status. The activity and output of lactotroph and somatotroph cells of the pituitary and their regulation by the hypothalamus is highly dynamic and dependent on physiological status. Using transgenic mice allowing identification and manipulation of pituitary cells and their regulatory hypothalamic neurones, we are dissecting the processes underlying the plasticity of pituitary output and its patterning. Studies to date have overturned accepted dogma that variation in pituitary cell number and altered hypothalamic regulation accounts for altered output. At the pituitary level, we have showing that homotypic cells are organized into distinct, characteristic motifs, which are modified by physiological status. These allow cell–cell communication, resulting in coordination and modification of responses to hypothalamic regulation. Remarkably, the reversibility of altered cell organization in response to physiological demand is also dependent on cell type: reorganization of lactotrophs during lactation is maintained following weaning and is associated with an enhanced output following the repeated demand of a further lactation. These pituitary-level changes do not dominate hypothalamic regulation: changes in the output of, for example tuberinfundibular dopamine neurones, must also occur to allow maintenance of high circulating prolactin concentrations required for lactation. To further study hypothalamic–pituitary functional relationships, novel tools and methodologies are required. The development and use of some of these will be described.