Variant estrogen and progesterone receptor messages in human vascular smooth muscle

Background-Estrogens stimulate growth of breast or uterine cells but have t he opposite effect on vascular smooth muscle cells. in which they protect a gainst coronary artery disease with ur without concomitant administration o f progesterone. A possible cause of differences in hormone action is variab le tissue-specific expression of hormone receptor. Therefore, we analyzed t he structure of estrogen receptors (ERs) and progesterone receptors (PRs) i n 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 tr anscriptase and polymerase chain reaction, Interestingly, in addition to wi ld-type ER-alpha and PR, 5 variant ER-alpha and 2 variant PR transcripts we re found. These variants contained precise deletions of exons encoding regi ons of the hormone-binding domain. The PR transcripts lacked exon 4 (PR Del ta 4) and exon 6 (PR Delta 6). The ER-alpha transcripts were missing exon 4 (ER Delta 4), exon 5 (ER Delta 5), exon 6 (ER Delta 6), exon 7 (ER Delta 7 ), and exons 6 and 7, (ER Delta 6,7). ER-beta variants were also detected. The PR variants were functionally characterized, and PR Delta 6 was found t o be a dominant-negative transcription inhibitor of wild-type receptors. Va riant PR was present in premenopausal women but absent in postmenopausal wo men. Conclusions-Variant PR and ER transcripts are extensively expressed in huma n vascular smooth muscle, The complex tissue-specific effects of sex hormon es may be mediated by the expression of heterogeneous fr,rms of their cogna te receptors. The presence of variant ERs and PRs may be of importance in a ltering the physiological effects of estrogens or progestins in vascular sm ooth muscle.