uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Estrogen-mediated regulation of CYP7B1: a possible role for controlling DHEA levels in human tissues
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2006 (English)In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 100, no 1-3, 42-51 p.Article in journal (Refereed) Published
Abstract [en]

The current study examines regulation of CYP7B1, a DHEA 7alpha-hydroxylase, by sex hormones. Transfection with estrogen receptor alpha and treatment with 17beta-estradiol in human embryonic kidney 293 cells significantly increased CYP7B1 catalytic activity and mRNA, and stimulated a human CYP7B1 reporter gene. Transfection with estrogen receptor beta showed similar but less significant effects. In the absence of receptors, 17beta-estradiol suppressed CYP7B1 activity, suggesting that estrogenic effects may be different in cells not expressing receptors. Quantitation of CYP7B1 mRNA in adult and fetal human tissues showed markedly higher CYP7B1 mRNA levels in fetal tissues compared with the corresponding adult ones, except in the liver. This indicates a tissue-specific, developmental regulation of CYP7B1 and suggests an important function for this enzyme in fetal life. DHEA secreted by fetal adrenals is an essential precursor for placental estrogen formation. Since CYP7B1 diverts DHEA from the sex hormone biosynthetic pathway, estrogen receptor-mediated up-regulation of CYP7B1 should lead to less DHEA available for sex hormone synthesis and may help to maintain normal levels of estrogens and androgens in human tissues, especially during fetal development. Regulation by estrogens may also be of importance in other processes where CYP7B1 is involved, including cholesterol homeostasis, cellular proliferation, and CNS function.

Place, publisher, year, edition, pages
2006. Vol. 100, no 1-3, 42-51 p.
Keyword [en]
estrogen, DHEA, CYP7B1, sex hormone biosynthesis, 7 alpha-hydroxylase, fetal development
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95810DOI: 10.1016/j.jsbmb.2006.02.005ISI: 000240161600006PubMedID: 16720094OAI: oai:DiVA.org:uu-95810DiVA: diva2:170155
Available from: 2007-04-27 Created: 2007-04-27 Last updated: 2011-06-20Bibliographically approved
In thesis
1. Hormonal Regulation of the Human CYP27A1 and CYP7B1 Genes
Open this publication in new window or tab >>Hormonal Regulation of the Human CYP27A1 and CYP7B1 Genes
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

CYP27A1 and CYP7B1 are widely expressed in various human tissues and are two key enzymes involved in the pathways for conversion of cholesterol to bile acids. Also, CYP27A1 is involved in bioactivation of vitamin D3 and CYP7B1 plays a role in 7alpha-hydroxylation of dehydroepiandrosterone and other steroids. Both enzymes have been reported to be relevant to prostate cell proliferation. The current study examines the hormonal regulation of CYP27A1 and CYP7B1.

CYP7B1 was shown to be regulated by estrogens and androgens in human embryonic kidney HEK293 and prostate cancer LNCaP cells. Quantitation of CYP7B1 mRNA in adult and fetal human tissues showed markedly higher CYP7B1 mRNA levels in fetal tissues compared with the corresponding adult ones, except in the liver. This indicates a tissue-specific, developmental regulation of CYP7B1 and suggests an important function for this enzyme in fetal life. CYP7B1 regulation by estrogens may be of importance in fetal development and in other processes where CYP7B1 is involved, including cholesterol homeostasis, cellular proliferation, and CNS function. The regulation of CYP7B1 by sex hormones also suggests an important role for CYP7B1 in balancing prostate hormone levels in human cells.

Results show that CYP27A1 can be regulated by dexamethasone, growth hormone, IGF-1, PMA, estrogens and androgens in liver-derived HepG2 cells. Dexamethasone, growth hormone and IGF-1 stimulated the promoter and endogenous activity of CYP27A1, whereas thyroid hormones and PMA inhibited CYP27A1. The regulatory effects of estrogens and androgens are different depending on the cell types. Thus, the results imply that human CYP27A1 gene is a target for estrogens and androgens, and the expression of CYP27A1 may be affected by endogenous sex hormones and pharmacological compounds with estrogenic or androgenic effects.

The mechanism for the dexamethasone-induced effect on the human CYP27A1 promoter was examined. A GRE was identified important for GR-mediated regulation of CYP27A1 transcriptional activity.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 56
Keyword
Pharmaceutical biochemistry, CYP27A1, CYP7B1, cholesterol, estrogen, androgen, prostate, glucocorticoid receptor, fetal development, Farmaceutisk biokemi
Identifiers
urn:nbn:se:uu:diva-7837 (URN)978-91-554-6876-7 (ISBN)
Public defence
2007-05-22, C2:301, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2007-04-27 Created: 2007-04-27Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Norlin, Maria

Search in DiVA

By author/editor
Norlin, Maria
By organisation
Department of Pharmaceutical Biosciences
In the same journal
Journal of Steroid Biochemistry and Molecular Biology
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 731 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf