RGD Reference Report - Genetic Bases of Estrogen-Induced Pituitary Tumorigenesis: Identification of Genetic Loci Determining Estrogen-Induced Pituitary Growth in Reciprocal Crosses between the ACI and Copenhagen Rat Strains. - Rat Genome Database

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Genetic Bases of Estrogen-Induced Pituitary Tumorigenesis: Identification of Genetic Loci Determining Estrogen-Induced Pituitary Growth in Reciprocal Crosses between the ACI and Copenhagen Rat Strains.

Authors: Strecker, TE  Spady, TJ  Schaffer, BS  Gould, KA  Kaufman, AE  Shen, F  McLaughlin, MT  Pennington, KL  Meza, JL  Shull, JD 
Citation: Strecker TE, etal., Genetics 2005 Jan 31;.
RGD ID: 1334449
Pubmed: PMID:15687265   (View Abstract at PubMed)
PMCID: PMC1449615   (View Article at PubMed Central)
DOI: DOI:10.1534/genetics.104.039370   (Journal Full-text)

Estrogens stimulate proliferation and enhance survival of the prolactin (PRL)-producing lactotroph of the anterior pituitary gland and induce development of PRL-producing pituitary tumors in certain inbred rat strains but not others. The goal of this study was to elucidate the genetic bases of estrogen-induced pituitary tumorigenesis in reciprocal intercrosses between the genetically related ACI and Copenhagen (COP) rat strains. Following 12 weeks of treatment with the synthetic estrogen diethylstilbestrol (DES), pituitary mass, an accurate surrogate marker of absolute lactotroph number, was increased 10.6-fold in ACI rats and 4.5-fold in COP rats. Composite interval mapping analyses of the phenotypically defined F2 progeny from the reciprocal crosses identified six quantitative trait loci (QTL) that determine the pituitary growth response to DES. These loci reside on chromosome 6, Ept1 (Estrogen-induced pituitary tumor); chromosome 3, Ept2 and Ept6; chromosome 10, Ept9; and chromosome 1, Ept10 and Ept13. Together, these 6 Ept loci and one additional suggestive locus on chromosome 4 account for an estimated 40% of the phenotypic variance exhibited by the combined F2 population, while 34% of the phenotypic variance was estimated to result from environmental factors. These data indicate that DES-induced pituitary mass behaves as a quantitative trait and provide information that will facilitate identification of genes that determine the tumorigenic response of the pituitary gland to estrogens.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ept1RatPituitary Neoplasms  IAGP  RGD 
Ept10RatPituitary Neoplasms  IAGP  RGD 
Ept13RatPituitary Neoplasms  IAGP  RGD 
Ept2RatPituitary Neoplasms  IAGP  RGD 
Ept6RatPituitary Neoplasms  IAGP  RGD 
Ept9RatPituitary Neoplasms  IAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ept1Ratpituitary gland hyperplasia  IAGP  RGD 
Ept10Ratpituitary gland hyperplasia  IAGP  RGD 
Ept13Ratpituitary gland hyperplasia  IAGP  RGD 
Ept2Ratpituitary gland hyperplasia  IAGP  RGD 
Ept6Ratpituitary gland hyperplasia  IAGP  RGD 
Ept9Ratpituitary gland hyperplasia  IAGP  RGD 

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Objects Annotated

QTLs
Ept1  (Estrogen-induced pituitary tumorigenesis QTL 1)
Ept10  (Estrogen-induced pituitary tumorigenesis QTL 10)
Ept13  (Estrogen-induced pituitary tumorigenesis QTL 13)
Ept2  (Estrogen-induced pituitary tumorigenesis QTL 2)
Ept6  (Estrogen-induced pituitary tumorigenesis QTL 6)
Ept9  (Estrogen-induced pituitary tumorigenesis QTL 9)

Strains
ACI/SegHsd  (NA)
COP/CrCrl  (NA)

Objects referenced in this article
Marker D6Rat150 D6Rat150 Rattus norvegicus

Additional Information