Functional heterogeneity among cell types in the normal pituitary gland and in human and rat pituitary tumors.

Hormone secretion by the anterior pituitary gland is under control of hypothalamic regulatory factorsjhormones (see chapter I.l) and peripheral hormones. Apart from the direct effects of these hormones on anterior pituitary hormone secretion several fine- regulatory mechanisms may play a role in determining the ultimate response of hormone secretion by the anterior pituitary to the hypothalamic or peripheral feedback hormones. These fine- regulatory mechanisms include paracrine effects between anterior pituitary cell types (see chapter I. 1. 2. 1) and functional heterogeneity within anterior pituitary cell types (see chapter I .1. 2. 2) . Whether these fine- regulatory mechanisms may also occur within human pituitary adenomas is not known (see chapter I.2.3). It has been suggested that differences in the hypothalamic input, due to a different intrapituitary localization of cell types, may be a basis for normal rat mammotrope heterogeneity. In addition it is not known whether a similar "mechanism" may cause functional heterogeneity as has been demonstrated within the normal rat somatotrope population (see chapter I. 1. 2. 2) . One of the aims of this thesis was to investigate whether normal rat mammotropes and somatotropes are functionally heterogeneous with respect to basal hormone release and responsiveness to secretagogues when cultured in the absence of hypothalamic influence, in order to provide additional evidence for the above hypothesis. In chapter III the results of experiments are described in which rat mammotrope and somatotrope subpopulations, separated according to differences in their density, were cultured during 7 days in the absence of hypothalamic hormones. Subsequently, these subpopulations were tested for their responses to the hypothalamic hormones which normally regulate the secretion of PRL and GH. As has been mentioned in chapter I. 2 functional heterogeneity of cells (cell types) within experimental rat pituitary tumors and within human pituitary tumors has not been studied extensively yet. The second aim of this thesis was to investigate whether functional heterogeneity exists among cells of pituitary adenomas. We have used for our studies two types of pituitary adenomas, an experimental prolactin-secreting rat pituitary tumor and human GHsecreting pituitary adenomas. In chapters IV, V and VI the results of experiments concerning intratumor heterogeneity of an experimental rat pituitary tumor {chapter IV) and of GHsecreting human pituitary adenomas {chapters v and VI) are described. In chapter VII the results of a study concerning heterogeneity between GH- secreting pituitary adenomas from acromegalic patients are presented