(Circulation. 1999;99:2688-2693.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Variant Estrogen and Progesterone Receptor Messages in Human Vascular Smooth Muscle
From the Department of Medicine, Division of Cardiology (Y.K.H., L.D.H.) and Division of Endocrinology (J.K.R., K.B.H.), University of Colorado Health Sciences Center, Denver, Colo.
Correspondence to Lawrence D. Horwitz, MD, Cardiology B130, University of Colorado Health Sciences Center, Denver, CO 80262. E-mail lawrence.horwitz{at}uchsc.edu
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-
and PR were characterized
by reverse transcriptase and polymerase chain reaction. Interestingly,
in addition to wild-type ER- and PR, 5 variant ER- 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 (PR
4) and exon 6 (PR6). The ER-
transcripts were missing exon 4 (ER4), exon 5 (ER5), exon 6
(ER6), exon 7 (ER7), and exons 6 and 7, (ER6,7). ER-ß
variants were also detected. The PR variants were functionally
characterized, and PR6 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.
Key Words: genes • muscle, smooth • receptors • hormones • coronary disease
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