ESTROGEN REG OF TGF/B IN PITUITARY TUMOR INDUCT &GROWTH

Project Details

Description

Estrogen has been implicated in the control of pituitary tumor induction
and growth in rats; the majority of these tumors involve prolactin (PRL)-
secreting lactotropes. The incidence of PRL-secreting pituitary tumors
(prolactinomas) is high in human patients, and increased tumor growth under
estrogenic influence in female patients is often of clinical concern. The
goal of this proposal is to determine the role of transforming growth
factor-beta1 (TGF-beta1) in the estrogen-regulated lactotropic (PRL-
secreting cells) secretion and growth, using the rat as an animal model.
The hypotheses to be tested are i) that TGF-beta1 inhibits lactotropic
secretion and proliferation by an autocrine/paracrine mechanism and ii)
that inhibition of pituitary TGF-beta1 activity is one of the mechanisms by
which estrogen induces neoplasm in the lactotrope. specific aims are to:
1) determine the action of TGF-beta1 in estrogen-regulated PRL secretion,
PRL mRNA expression and lactotropic proliferation; 2) elucidate estrogen
effects on TGF-beta1 protein production and secretion; 3) evaluate estrogen
action on TGF-beta1 mRNA expressions in the pituitary; 4) understand the
interaction between estrogen, TGF-beta1 and PRL at the level of gene
transcription. Several technological approaches will be utilized to
achieve these aims. These will include: a) cell cultures of normal and
tumor pituitaries; b) the identification of TGF-beta1 producing cells in
the pituitary gland by using immunohistochemistry and in situ hybridization
procedures; c) the measurement of TGF-beta1 and PRL secretion in the
pituitary by specific radioimmunoassays; d) the determination of pituitary
cell proliferation by using a bromodeoxyuridine incorporation assay, e) the
assay of TGF-beta1 and PRL mRNA levels using northern blot and in situ
hybridization techniques, f) the study of the interaction between TGF-
beta1, estrogen and PRL at the gene level by nuclear run on transcription
and mRNA stability assays. The proposed research will yield an increased understanding of the
mechanisms involved in estrogen-induced abnormalities in the function and
growth of lactotropes. Such understanding should provide new clues to the
process involved in the formation of prolactinomas.
StatusFinished
Effective start/end date8/1/927/31/96

Funding

  • National Institutes of Health
  • National Institutes of Health: $128,236.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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