NEUROENDOCRINE MECHANISMS OF PROLACTINOMAS IN OLD RATS

Project Details

Description

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.
StatusFinished
Effective start/end date9/30/851/31/89

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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