Document Detail


Variant estrogen and progesterone receptor messages in human vascular smooth muscle.
MedLine Citation:
PMID:  10338464     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Estrogens stimulate growth of breast or uterine cells but have the opposite effect on vascular smooth muscle cells, in which they protect against coronary artery disease with or without concomitant administration of progesterone. A possible cause of differences in hormone action is variable tissue-specific expression of hormone receptor. Therefore, we analyzed the structure of estrogen receptors (ERs) and progesterone receptors (PRs) in human vascular smooth muscle. METHODS AND RESULTS: RNA was isolated from human vascular smooth muscle, and the functional domains of ER-alpha and PR were characterized by reverse transcriptase and polymerase chain reaction. Interestingly, in addition to wild-type ER-alpha and PR, 5 variant ER-alpha and 2 variant PR transcripts were found. These variants contained precise deletions of exons encoding regions of the hormone-binding domain. The PR transcripts lacked exon 4 (PRDelta4) and exon 6 (PRDelta6). The ER-alpha transcripts were missing exon 4 (ERDelta4), exon 5 (ERDelta5), exon 6 (ERDelta6), exon 7 (ERDelta7), and exons 6 and 7, (ERDelta6,7). ER-beta variants were also detected. The PR variants were functionally characterized, and PRDelta6 was found to be a dominant-negative transcription inhibitor of wild-type receptors. Variant PR was present in premenopausal women but absent in postmenopausal women. CONCLUSIONS: Variant PR and ER transcripts are extensively expressed in human vascular smooth muscle. The complex tissue-specific effects of sex hormones may be mediated by the expression of heterogeneous forms of their cognate receptors. The presence of variant ERs and PRs may be of importance in altering the physiological effects of estrogens or progestins in vascular smooth muscle.
Authors:
Y K Hodges; J K Richer; K B Horwitz; L D Horwitz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  99     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-06-15     Completed Date:  1999-06-15     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2688-93     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver, Colo. 80262, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Culture Techniques
Estrogen Receptor beta
Exons / genetics
Female
Gene Deletion
Genetic Variation* / physiology
Humans
Male
Middle Aged
Muscle, Smooth, Vascular / metabolism*
Postmenopause / metabolism
Premenopause / metabolism
RNA, Messenger / metabolism*
Receptors, Estrogen / genetics*
Receptors, Progesterone / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
CA-26869/CA/NCI NIH HHS; DK-48238/DK/NIDDK NIH HHS; HL-55291/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Estrogen Receptor beta; 0/RNA, Messenger; 0/Receptors, Estrogen; 0/Receptors, Progesterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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