EDRI Federal Project Inventory:
60698-03 Role of VIP in Estrogen-induced Prolactinomas
- Sponsor Organization: NIH/NCI
- Project Title: 60698-03 ROLE OF VIP IN ESTROGEN-INDUCED PROLACTINOMAS
- Project Focus: HUMAN HEALTH EFFECTS
- Description: The most common secretory hypothalamic-pituitary disorders encountered
in clinical reproductive endocrinology arethose associated with
hyperprolactinemia. Hyperprolactinemia accounts for at least 20104f
infertility in women and atleast 8111f sexual dysfunction in men,
including infertility. The etiologies of pathological
hyperprolactinemia arediverse, but by far the most common cause is a
pituitary tumor. The pathogenesis of prolactinomas has yet to be
defined. Since most prolactin (PRL)-secreting tumors occur in
premenopausal women and exhibit growth in the presence ofestrogens,
the rat model of diethylstilbestrol (DES)-induced tumors is an
excellent model for the study of the mechanismof prolactinoma
formation. Several studies revealed intrapituitary vasoactive
intestinal polypeptide (VIP) tissue contentand mRNA increases
significantly in these estrogen-induced rat prolactinomas.
Additionally, exogenous andendogenous VIP is a well known stimulator
of PRL release from pituitary tissue in vivo and in vitro. This
laboratoryfound immunoneutralization of intrapituitary VIP with VIP
antiserum (AVIP) significantly decreased PRL mRNA indispersed rat DES
tumor cells. The goal of this project is to focus on this
relationship between estrogen and VIP in theformation of
prolactinomas. The central hypothesis of this application is VIP
plays an important intermediary role inthe pathogenesis of DES-induced
prolactinomas. The specific aims developed to test this hypothesis
include: I. Todetermine if the significant reduction in rPRL mRNA
from dispersed DES-induced prolactinoma cells incubated inAVIP is due
to an effect on PRL gene transcription, mRNA degradation, or both.
II. To determine if the significantreduction in rPRL mRNA from
dispersed DES-induced prolactinoma cells incubated in AVIP is observed
after longerperiods of DES exposure. III. To determine how other
known PRL regulators, TRH and dopamine, affect the anteriorpituitary
VIP tissue content and mRNA in the DES-induced tumor model. IV. To
determine whether the formation ofthese estrogen-induced prolactinomas
can be prevented by inhibition of VIP.
- References:
- Category: MODELS
- Subcategory: BASIC RESEARCH
- Keywords for Experimental System/Species: LABORATORY STUDY, IN VIVO, IN VITRO
- Keywords for Experimental Endpoints: PEPTIDE HORMONES, GROWTH, CARCINOGENESIS
- Chemical Agents: ESTROGEN, DIETHYLSTILBESTROL (DES)
- Performing Institution: MEDICAL COLLEGE OF WISCONSIN
- Contact: CONTACT PERSON: ELAINE C. LEE; BUILDING 31; 11A21, NATIONAL CANCER
INSTITUTE, NIH,BETHESDA, MD 20892-2590; 301 496-5515;
LEEE@0D.NCI.NIH.GOV
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