Galanin in the pituitary and in human circulation : clinical and experimental studies

Abstract: The neuropeptide galanin has important roles in the central and peripheral nervous systems where it affects memory, seizure activity, appetite and pain transmission. Galanin is also present in the endocrine system and one of its most prominent effects is to stimulate the release of growth hormone (GH). Galanin also stimulates pituitary tumour formation in the rat. The aims of this thesis were to study galanin actions on the pituitary of the rat as well as its presence in human pituitary adenomas and in the human circulation. In order to do this, a radioimmunoassay (RIA) for human galanin was developed. With this RIA, human galanin can be measured in levels down to 1 pmo1/L. Galanin was found in extracts from human pituitary adenomas with high levels in ACTHsecreting adenomas, moderate and varying levels in clinically inactive adenomas and low levels in GH-secreting adenomas. Galanin and ACTH levels were positively correlated in these tumour extracts. Galanin and ACTH were found to be colocalized in some single cells by double in situ hybridization. In tumour extracts, molecular mass forms of galanin immunoreactivity were homogeneous and corresponded to synthetic human galanin. Immunoreactive galanin was characterized in plasma and was found to be present in heterogeneous molecular forms, the majority being homologs of higher molecular weight but smaller forms were also present. The higher molecular forms, present after immunoaffinity separation, were eliminated by extraction on reversed phase minicolumns. Plasma levels of galanin after extraction were found to be higher in a small group of healthy men compared to healthy women. In spite of the presence of galanin ACTH-secreting cells of the human pituitary, galanin in plasma was not increased in patients with pituitary hypersecretion of ACTH In patients with Cushing's disease normal galanin levels were found in peripheral plasma as well as in pituitary effluent blood. Despite considerable elevation of plasma ACTH in a subset of patients with Addison's disease, no elevation of plasma galanin was found. In vitro experiments on rat pituitary cells in culture showed inhibition by galanin on GHRH-stimulated secretion of GH. In conclusion, the establishment of a specific assay for galanin opens the possibility to measure galanin in human tissue and body fluids. Galanin has multiple roles in physiology. Its role in a number of pathological states, in particular in pituitary function and tumour formation should be further explored.