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Estrogen receptor gene expression in human uterine leiomyomata.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 1995 Jun; Vol. 80 (6), pp. 1876-81. - Publication Year :
- 1995
-
Abstract
- Estrogen and progestin are believed to be important physiological regulators of uterine leiomyoma growth. We recently showed that progesterone receptor messenger ribonucleic acid (mRNA) and protein levels are increased in human uterine leiomyomas compared with those in myometrial biopsy tissue obtained from the same patient. To further characterize the molecular mechanisms underlying abnormal growth of uterine leiomyomas, we analyzed biopsy samples of tumor and adjacent normal myometrium for estrogen receptor (ER) gene expression. Northern analysis indicated that ER mRNA levels were increased 1.4-to 12.6-fold in leiomyoma compared with myometrium in all patients examined (n = 11), whereas beta-actin mRNA was not different between the two groups. The size of the primary ER mRNA transcript was 6.2 kilobases in both leiomyoma and myometrium, indicating no gross mutation of the ER gene. An ER protein of 66 kilodaltons was detected by Western blot analysis, and quantitative immunoassay of ER revealed 9448 +/- 1955 fmol/mg DNA in leiomyoma compared to 2827 +/- 979 fmol/mg DNA in myometrial tissue. Scatchard analysis of 17 beta-estradiol binding to cell-free extracts revealed enhanced binding capacity (per mg DNA) in leiomyoma tissue (n = 6) of about 6-fold, whereas ER binding affinity was not substantially different between the leiomyoma and adjacent myometrial tissues. We propose that increased expression of progesterone receptor in leiomyoma is most likely a consequence of overexpression of functional ER that results in increased end-organ sensitivity to estradiol.
- Subjects :
- Adult
Biopsy
Blotting, Northern
Blotting, Western
Cytosol metabolism
DNA, Neoplasm analysis
Estradiol metabolism
Female
Humans
Immunoenzyme Techniques
Middle Aged
Myometrium metabolism
RNA, Messenger metabolism
Gene Expression
Leiomyoma metabolism
Receptors, Estrogen genetics
Uterine Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-972X
- Volume :
- 80
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 7775635
- Full Text :
- https://doi.org/10.1210/jcem.80.6.7775635