The specific aims are to investigate the neuroendocrine mechanisms involved in the development of prolactin-secreting pituitary tumors, using the rat as an animal model. Pituitary tumors are commonly found in rats in old age and after prolonged estrogen treatment; the majority of these tumors involve prolactin-secreting cells. On the working assumption that hypothalamic dopamine is a significant prolactin-inhibiting factor (PIF), and hypothalamic thyrotropic-releasing hormone, vasoactive intestinal peptide, and oxytocin are significant prolactin release-stimulating factors (PRFs), the proposed experiments will examine the relative levels of rat pituitary prolactin and hypothalamic and pituitary portal blood PIF and PRFs in two situations where a high incidence of pituitary tumors is found: old age and long-term estrogen treatment. The effect of these hypothalamic substances on the growth and prolactin secretion of the pituitary gland will be evaluated. The effect of biochemical lesions destroying the dopaminergic neurons in the hypothalamus on prolactinomas will be determined in both old and estrogen-treated young rats. A study will also be undertaken to determine whether transplants of fetal mesencepalon or hypothalamus to the third ventricle overcome the functional loss of hypothalamic neurons and decrease the incidence and growth of prolactinomas. Peptide concentrations in the blood and in the tissue will be determined by RIA. Dopaminergic neuronal functions will be determined by fluorescence histochemistry and radioenzymatic assay of dopamine. Histological methods will be employed to determine morphological changes in the hypothalamus and pituitary. The weight and DNA content of the pituitary will be assayed for determining the growth of the pituitary. These studies are believed to form a basis for the understanding of commonly occurring prolactinomas in human patients.
