1. Endocrinology. 2008 Aug;149(8):3850-9. doi: 10.1210/en.2008-0173. Epub 2008 Apr
17.
Tissue-specific actions of the Ept1, Ept2, Ept6, and Ept9 genetic determinants of
responsiveness to estrogens in the female rat.
Kurz SG(1), Hansen KK, McLaughlin MT, Shivaswamy V, Schaffer BS, Gould KA, McComb
RD, Meza JL, Shull JD.
Author information:
(1)Department of Genetics, Cell Biology and Anatomy, 6005 Durham Research Center,
985805 Nebraska Medical Center, Omaha, Nebraska 68198-5805, USA.
Ept1, Ept2, Ept6, and Ept9 are quantitative trait loci mapped in crosses between
the ACI and Copenhagen (COP) rat strains as genetic determinants of
responsiveness of the pituitary gland to estrogens. We have developed four
congenic rat strains, each of which carries, on the genetic background of the ACI
rat strain, alleles from the COP rat strain that span one of these quantitative
trait loci. Relative to the female ACI rats, female ACI.COP-Ept1 rats exhibited
reduced responsiveness to 17beta-estradiol (E2) in the pituitary gland, as
evidenced by quantification of pituitary mass and circulating prolactin, and in
the mammary gland, as evidenced by reduced susceptibility to E2-induced mammary
cancer. The ACI.COP-Ept2 rat strain exhibited reduced responsiveness to E2 in the
pituitary gland but did not differ from the ACI strain in regard to
susceptibility to E2-induced mammary cancer. Interestingly, female Ept2 congenic
rats exhibited increased responsiveness to E2 in the thymus, as evidenced by
enhanced thymic atrophy. The ACI.COP-Ept6 rat strain exhibited increased
responsiveness to E2 in the pituitary gland, which was associated with a
qualitative phenotype suggestive of enhanced pituitary vascularization. The
ACI.COP-Ept9 rat strain exhibited reduced responsiveness to E2 in the anterior
pituitary gland, relative to the ACI rat strain. Neither Ept6 nor Ept9 impacted
responsiveness to E2 in the mammary gland or thymus. These data indicate that
each of these Ept genetic determinants of estrogen action is unique in regard to
the tissues in which it exerts its effects and/or the direction of its effect on
estrogen responsiveness.
PMCID: PMC2488241
PMID: 18420736 [PubMed - indexed for MEDLINE]
PUBMED: 18420736
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