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In vivo response-based identification of direct hormone target cell populations using high-density tissue arrays. Endocrinology 2007 Mar;148(3):989-1008

Date

12/02/2006

Pubmed ID

17138649

DOI

10.1210/en.2006-1219

Scopus ID

2-s2.0-33847059271   27 Citations

Abstract

To identify cell populations directly responsive to prolactin (PRL), GH, erythropoietin, or granulocyte-colony stimulating factor within the physiological setting of an intact mammal, we combined in situ detection of hormone-activated signal transducer and activator of transcription (Stat)-5 in rats with high-throughput tissue array analysis using cutting-edge matrix assembly (CEMA). Inducible activation of Stat5a/b, as judged by levels of nuclear-localized, phosphoTyr694/699-Stat5a/b, served as an immediate and sensitive in situ marker of receptor signaling in rat tissues after injection into male and female rats of a single, receptor-saturating dose of hormone for maximal receptor activation. CEMA tissue arrays facilitated analysis of most tissues, including architecturally complex, thin-walled, and stratified tissues such as gut and skin. In 40 tissues analyzed, 35 PRL-responsive and 32 GH-responsive cell types were detected, of which 22 cell types were responsive to both hormones. Interestingly, PRL but not GH activated Stat5 in nearly all of the endocrine glands. In mammary glands, PRL activated Stat5 in a majority of luminal epithelial cells but not myoepithelial cells, stromal fibroblasts, or adipocytes, whereas GH activated Stat5 in a significant fraction of myoepithelial cells, fibroblasts, and adipocytes but only in a minority of luminal cells. Finally, the organism-wide screening revealed a yet-to-be identified erythropoietin-responsive cell type in connective tissue. CEMA tissue arrays provide cost-effective in situ analysis of large numbers of tissues. Biomarker-based identification of cell populations responsive to individual hormones may shed new light on endocrine disease as well as improve understanding of effects and side effects of hormones and drugs.

Author List

LeBaron MJ, Ahonen TJ, Nevalainen MT, Rui H

Authors

Marja T. Nevalainen MD, PhD Assistant Dean, Professor in the Pathology department at Medical College of Wisconsin
Hallgeir Rui MD, PhD Vice Chair, Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Endocrine Glands
Erythropoietin
Female
Gene Expression
Gonads
Granulocyte-Macrophage Colony-Stimulating Factor
Growth Hormone
In Situ Hybridization
Islets of Langerhans
Male
Organ Specificity
Prolactin
Rats
Rats, Sprague-Dawley
STAT5 Transcription Factor
Signal Transduction
Tissue Array Analysis
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc