Cellular localization of estradiol-induced c-fos messenger ribonucleic acid in the rat uterus: c-fos expression and uterine cell proliferation do not correlate strictly

Kenneth Nephew, G. A. Peters, S. A. Khan

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43 Citations (Scopus)

Abstract

Estrogens stimulate DNA synthesis and cell proliferation in the uterus. All major uterine cell types (luminal and glandular epithelium, stroma, and myometrium) respond to 17β-estradiol in the immature animal, whereas primarily epithelial cells of the uterine endometrium respond in the mature animal. Rapid activation of the c-fos protooncogene by estrogen precedes the uterine growth, suggesting that c-fos plays a role in amplifying the hormonal signal. The specific uterine cell types in which estrogen induces c-fos messenger RNA (mRNA) expression, however, have not been identified in either mature or immature animals. In this study, in situ hybridization was used to determine the cell type-specific location of mRNA encoding c-fos in the uterus. In both immature and mature castrated rats at 3 h after 17β- estradiol administration, c-fos expression was detected primarily in uterine luminal and glandular epithelia. Expression of c-fos returned to baseline levels by 24 h post 17β-estradiol treatment. There was no apparent difference in the uterine cell type-specific pattern of c-fos expression stimulated by estradiol in mature vs. immature animals. Nuclear run-on transcription assay in isolated luminal epithelial cell nuclei showed that c- fos gene transcription increased rapidly in the uterus after estradiol stimulation. Treatment of adult rats with a single injection of 16α- estradiol, a short-acting, nonmitogenic estrogen, induced c-fos primarily in the uterine glandular epithelia. Progesterone is known to modify the action of estrogen on the uterus by redirecting the proliferative response from epithelia to stroma. To determine if progesterone modulation of estrogen action involves shifting of c-fos expression to stromal cells, rats were treated with progesterone for 48 h and then killed 0, 3, 6, or 12 h after an estradiol injection. In situ hybridization analysis revealed that c-fos mRNA remained localized in the uterine luminal and glandular epithelia, and expression was not shifted to the stroma. Although these results support the idea that c-fos plays a role in proliferation of uterine epithelial cells, they also invite reassessment of the role played by c-fos in both epithelial and nonepithelial uterine cell types.

Original languageEnglish (US)
Pages (from-to)3007-3015
Number of pages9
JournalEndocrinology
Volume136
Issue number7
StatePublished - 1995
Externally publishedYes

Fingerprint

Uterus
Estradiol
Estrogens
Cell Proliferation
RNA
Epithelium
Progesterone
Epithelial Cells
Messenger RNA
In Situ Hybridization
fos Genes
Injections
Myometrium
Stromal Cells
Endometrium
Cell Nucleus
DNA
Therapeutics
Growth

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{9bb8cd60416a483ca0cec7e579c71158,
title = "Cellular localization of estradiol-induced c-fos messenger ribonucleic acid in the rat uterus: c-fos expression and uterine cell proliferation do not correlate strictly",
abstract = "Estrogens stimulate DNA synthesis and cell proliferation in the uterus. All major uterine cell types (luminal and glandular epithelium, stroma, and myometrium) respond to 17β-estradiol in the immature animal, whereas primarily epithelial cells of the uterine endometrium respond in the mature animal. Rapid activation of the c-fos protooncogene by estrogen precedes the uterine growth, suggesting that c-fos plays a role in amplifying the hormonal signal. The specific uterine cell types in which estrogen induces c-fos messenger RNA (mRNA) expression, however, have not been identified in either mature or immature animals. In this study, in situ hybridization was used to determine the cell type-specific location of mRNA encoding c-fos in the uterus. In both immature and mature castrated rats at 3 h after 17β- estradiol administration, c-fos expression was detected primarily in uterine luminal and glandular epithelia. Expression of c-fos returned to baseline levels by 24 h post 17β-estradiol treatment. There was no apparent difference in the uterine cell type-specific pattern of c-fos expression stimulated by estradiol in mature vs. immature animals. Nuclear run-on transcription assay in isolated luminal epithelial cell nuclei showed that c- fos gene transcription increased rapidly in the uterus after estradiol stimulation. Treatment of adult rats with a single injection of 16α- estradiol, a short-acting, nonmitogenic estrogen, induced c-fos primarily in the uterine glandular epithelia. Progesterone is known to modify the action of estrogen on the uterus by redirecting the proliferative response from epithelia to stroma. To determine if progesterone modulation of estrogen action involves shifting of c-fos expression to stromal cells, rats were treated with progesterone for 48 h and then killed 0, 3, 6, or 12 h after an estradiol injection. In situ hybridization analysis revealed that c-fos mRNA remained localized in the uterine luminal and glandular epithelia, and expression was not shifted to the stroma. Although these results support the idea that c-fos plays a role in proliferation of uterine epithelial cells, they also invite reassessment of the role played by c-fos in both epithelial and nonepithelial uterine cell types.",
author = "Kenneth Nephew and Peters, {G. A.} and Khan, {S. A.}",
year = "1995",
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pages = "3007--3015",
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AU - Khan, S. A.

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N2 - Estrogens stimulate DNA synthesis and cell proliferation in the uterus. All major uterine cell types (luminal and glandular epithelium, stroma, and myometrium) respond to 17β-estradiol in the immature animal, whereas primarily epithelial cells of the uterine endometrium respond in the mature animal. Rapid activation of the c-fos protooncogene by estrogen precedes the uterine growth, suggesting that c-fos plays a role in amplifying the hormonal signal. The specific uterine cell types in which estrogen induces c-fos messenger RNA (mRNA) expression, however, have not been identified in either mature or immature animals. In this study, in situ hybridization was used to determine the cell type-specific location of mRNA encoding c-fos in the uterus. In both immature and mature castrated rats at 3 h after 17β- estradiol administration, c-fos expression was detected primarily in uterine luminal and glandular epithelia. Expression of c-fos returned to baseline levels by 24 h post 17β-estradiol treatment. There was no apparent difference in the uterine cell type-specific pattern of c-fos expression stimulated by estradiol in mature vs. immature animals. Nuclear run-on transcription assay in isolated luminal epithelial cell nuclei showed that c- fos gene transcription increased rapidly in the uterus after estradiol stimulation. Treatment of adult rats with a single injection of 16α- estradiol, a short-acting, nonmitogenic estrogen, induced c-fos primarily in the uterine glandular epithelia. Progesterone is known to modify the action of estrogen on the uterus by redirecting the proliferative response from epithelia to stroma. To determine if progesterone modulation of estrogen action involves shifting of c-fos expression to stromal cells, rats were treated with progesterone for 48 h and then killed 0, 3, 6, or 12 h after an estradiol injection. In situ hybridization analysis revealed that c-fos mRNA remained localized in the uterine luminal and glandular epithelia, and expression was not shifted to the stroma. Although these results support the idea that c-fos plays a role in proliferation of uterine epithelial cells, they also invite reassessment of the role played by c-fos in both epithelial and nonepithelial uterine cell types.

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