Genetic control of estrogen action in the rat

Mapping of QTLs that impact pituitary lactotroph hyperplasia in a BN x ACI intercross

James D. Shull, Cynthia M. Lachel, Clare R. Murrin, Karen L. Pennington, Beverly S. Schaffer, Tracy E. Strecker, Karen A Gould

Research output: Contribution to journalArticle

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Abstract

Estrogens are important regulators of growth and development and contribute to the etiology of several types of cancer. Different inbred rat strains exhibit marked, cell-type-specific differences in responsiveness to estrogens as well as differences in susceptibility to estrogen-induced tumorigenesis. Regulation of pituitary lactotroph homeostasis is one estrogen-regulated response that differs dramatically between different inbred rat strains. In this article we demonstrate that the growth response of the anterior pituitary gland of female ACI rats to 17β-estradiol (E2) markedly exceeds that of identically treated female Brown Norway (BN) rats. We further demonstrate that pituitary mass, a surrogate indicator of absolute lactotroph number, behaves as a quantitative trait in E2-treated F2 progeny generated in a genetic cross originating with BN females and ACI males. Composite interval mapping analyses of the (BNxACI)F2 population revealed quantitative trait loci (QTLs) that exert significant effects on E2-induced pituitary growth on rat chromosome 4 (RNO4) (Ept5) and RNO7 (Ept7). Continuous treatment with E2 rapidly induces mammary cancer in female ACI rats but not BN rats, and QTLs that impact susceptibility to E2-induced mammary cancer in the (BNxACI)F2 population described here have been mapped to RNO3 (Emca5), RNO4 (Emca6), RNO5 (Emca8), RNO6 (Emca7), and RNO7 (Emca4). Ept5 and Emca6 map to distinct regions of RNO4. However, Ept7 and Emca4 map to the same region of RNO7. No correlation between pituitary mass and mammary cancer number at necropsy was observed within the (BNxACI)F2 population. This observation, together with the QTL mapping data, indicate that with the exception of the Ept7/Emca4 locus on RNO7, the genetic determinants of E2-induced pituitary growth differ from the genetic determinants of susceptibility to E2-induced mammary cancer.

Original languageEnglish (US)
Pages (from-to)657-669
Number of pages13
JournalMammalian Genome
Volume18
Issue number9
DOIs
StatePublished - Sep 1 2007

Fingerprint

Lactotrophs
Quantitative Trait Loci
Norway
Hyperplasia
Estrogens
Inbred ACI Rats
Inbred Strains Rats
Breast Neoplasms
Growth
Genetic Crosses
Population
Chromosomes, Human, Pair 4
Anterior Pituitary Gland
Pituitary Neoplasms
Genetic Predisposition to Disease
Growth and Development
Estradiol
Carcinogenesis
Homeostasis
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

Genetic control of estrogen action in the rat : Mapping of QTLs that impact pituitary lactotroph hyperplasia in a BN x ACI intercross. / Shull, James D.; Lachel, Cynthia M.; Murrin, Clare R.; Pennington, Karen L.; Schaffer, Beverly S.; Strecker, Tracy E.; Gould, Karen A.

In: Mammalian Genome, Vol. 18, No. 9, 01.09.2007, p. 657-669.

Research output: Contribution to journalArticle

Shull, James D. ; Lachel, Cynthia M. ; Murrin, Clare R. ; Pennington, Karen L. ; Schaffer, Beverly S. ; Strecker, Tracy E. ; Gould, Karen A. / Genetic control of estrogen action in the rat : Mapping of QTLs that impact pituitary lactotroph hyperplasia in a BN x ACI intercross. In: Mammalian Genome. 2007 ; Vol. 18, No. 9. pp. 657-669.
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