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 presente