Regulation of estrogen biosynthesis in human adipose stromal cells. Effects of dibutyryl cyclic AMP, epidermal growth factor, and phorbol esters on the synthesis of aromatase cytochrome P-450

C. T. Evans, C. J. Corbin, C. T. Saunders, J. C. Merrill, E. R. Simpson, C. R. Mendelson

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Using human adipose stromal cells in monolayer culture as a model system for study of the regulation of aromatase activity, as well as polyclonal antibodies raised in this laboratory against aromatase cytochrome P-450 (cytochrome P-450(AROM)), it was found that the rate of synthesis of cytochrome P-450(AROM) was stimulated by dibutyryl cyclic AMP. This stimulation was attenuated by epidermal growth factor and was potentiated by phorbol esters. These changes in cytochrome P-450(AROM) synthesis were associated with comparable changes in the levels of translatable cytochrome P-450(AROM) mRNA, as well as with changes in the activity or aromatase of these cells. By contrast, there was little change in the synthesis of the reductase component of the aromatase enzyme complex in response to these factors. The increase in mRNA was blocked by cycloheximide, indicative of a requirement for protein synthesis in mediating this inductive response. It is concluded that aromatase activity is regulated primarily by changes in the level of mRNA encoding cytochrome P-450(AROM), and that such changes are likely to a reflection of changes in the rate of transcription of the gene encoding this enzyme. Increases in the levels of cytochrome P-450(AROM) mRNA are apparently mediated by a regulatory protein(s), similar to that found for other steroidogenic forms of cytochrome P-450.

Original languageEnglish (US)
Pages (from-to)6914-6920
Number of pages7
JournalJournal of Biological Chemistry
Volume262
Issue number14
StatePublished - 1987

Fingerprint

Bucladesine
Aromatase
Biosynthesis
Phorbol Esters
Stromal Cells
Epidermal Growth Factor
Cytochrome P-450 Enzyme System
Estrogens
Messenger RNA
Gene encoding
Enzymes
Transcription
Cycloheximide
Monolayers
Oxidoreductases
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of estrogen biosynthesis in human adipose stromal cells. Effects of dibutyryl cyclic AMP, epidermal growth factor, and phorbol esters on the synthesis of aromatase cytochrome P-450. / Evans, C. T.; Corbin, C. J.; Saunders, C. T.; Merrill, J. C.; Simpson, E. R.; Mendelson, C. R.

In: Journal of Biological Chemistry, Vol. 262, No. 14, 1987, p. 6914-6920.

Research output: Contribution to journalArticle

@article{f93c3afce7e5481b8b37b1d0a4d09cac,
title = "Regulation of estrogen biosynthesis in human adipose stromal cells. Effects of dibutyryl cyclic AMP, epidermal growth factor, and phorbol esters on the synthesis of aromatase cytochrome P-450",
abstract = "Using human adipose stromal cells in monolayer culture as a model system for study of the regulation of aromatase activity, as well as polyclonal antibodies raised in this laboratory against aromatase cytochrome P-450 (cytochrome P-450(AROM)), it was found that the rate of synthesis of cytochrome P-450(AROM) was stimulated by dibutyryl cyclic AMP. This stimulation was attenuated by epidermal growth factor and was potentiated by phorbol esters. These changes in cytochrome P-450(AROM) synthesis were associated with comparable changes in the levels of translatable cytochrome P-450(AROM) mRNA, as well as with changes in the activity or aromatase of these cells. By contrast, there was little change in the synthesis of the reductase component of the aromatase enzyme complex in response to these factors. The increase in mRNA was blocked by cycloheximide, indicative of a requirement for protein synthesis in mediating this inductive response. It is concluded that aromatase activity is regulated primarily by changes in the level of mRNA encoding cytochrome P-450(AROM), and that such changes are likely to a reflection of changes in the rate of transcription of the gene encoding this enzyme. Increases in the levels of cytochrome P-450(AROM) mRNA are apparently mediated by a regulatory protein(s), similar to that found for other steroidogenic forms of cytochrome P-450.",
author = "Evans, {C. T.} and Corbin, {C. J.} and Saunders, {C. T.} and Merrill, {J. C.} and Simpson, {E. R.} and Mendelson, {C. R.}",
year = "1987",
language = "English (US)",
volume = "262",
pages = "6914--6920",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "14",

}

TY - JOUR

T1 - Regulation of estrogen biosynthesis in human adipose stromal cells. Effects of dibutyryl cyclic AMP, epidermal growth factor, and phorbol esters on the synthesis of aromatase cytochrome P-450

AU - Evans, C. T.

AU - Corbin, C. J.

AU - Saunders, C. T.

AU - Merrill, J. C.

AU - Simpson, E. R.

AU - Mendelson, C. R.

PY - 1987

Y1 - 1987

N2 - Using human adipose stromal cells in monolayer culture as a model system for study of the regulation of aromatase activity, as well as polyclonal antibodies raised in this laboratory against aromatase cytochrome P-450 (cytochrome P-450(AROM)), it was found that the rate of synthesis of cytochrome P-450(AROM) was stimulated by dibutyryl cyclic AMP. This stimulation was attenuated by epidermal growth factor and was potentiated by phorbol esters. These changes in cytochrome P-450(AROM) synthesis were associated with comparable changes in the levels of translatable cytochrome P-450(AROM) mRNA, as well as with changes in the activity or aromatase of these cells. By contrast, there was little change in the synthesis of the reductase component of the aromatase enzyme complex in response to these factors. The increase in mRNA was blocked by cycloheximide, indicative of a requirement for protein synthesis in mediating this inductive response. It is concluded that aromatase activity is regulated primarily by changes in the level of mRNA encoding cytochrome P-450(AROM), and that such changes are likely to a reflection of changes in the rate of transcription of the gene encoding this enzyme. Increases in the levels of cytochrome P-450(AROM) mRNA are apparently mediated by a regulatory protein(s), similar to that found for other steroidogenic forms of cytochrome P-450.

AB - Using human adipose stromal cells in monolayer culture as a model system for study of the regulation of aromatase activity, as well as polyclonal antibodies raised in this laboratory against aromatase cytochrome P-450 (cytochrome P-450(AROM)), it was found that the rate of synthesis of cytochrome P-450(AROM) was stimulated by dibutyryl cyclic AMP. This stimulation was attenuated by epidermal growth factor and was potentiated by phorbol esters. These changes in cytochrome P-450(AROM) synthesis were associated with comparable changes in the levels of translatable cytochrome P-450(AROM) mRNA, as well as with changes in the activity or aromatase of these cells. By contrast, there was little change in the synthesis of the reductase component of the aromatase enzyme complex in response to these factors. The increase in mRNA was blocked by cycloheximide, indicative of a requirement for protein synthesis in mediating this inductive response. It is concluded that aromatase activity is regulated primarily by changes in the level of mRNA encoding cytochrome P-450(AROM), and that such changes are likely to a reflection of changes in the rate of transcription of the gene encoding this enzyme. Increases in the levels of cytochrome P-450(AROM) mRNA are apparently mediated by a regulatory protein(s), similar to that found for other steroidogenic forms of cytochrome P-450.

UR - http://www.scopus.com/inward/record.url?scp=0023189829&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023189829&partnerID=8YFLogxK

M3 - Article

VL - 262

SP - 6914

EP - 6920

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 14

ER -