Abstract
Anti-estrogen therapies for treating ovarian carcinoma have had mixed outcomes suggesting some tumors may be estrogen-dependent. We assayed the activity levels of 17β-hydroxysteroid dehydrogenase (17β-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), 3α-hydroxysteroid dehydrogenase (3α-HSD/3-KSR) and estrone sulfatase in a series of ovarian epithelial carcinomas. 17β-HSD activity ratios with estradiol (E 2 ) and testosterone (T), and inhibition by isoform-specific inhibitors were used to estimate the contributions of 17β-HSD isoforms. Activity levels were highest for estrone sulfatase, followed, respectively by 17β-HSD, 3α-HSD/3-KSR, and 3β-HSD. E 2 /T activity ratios varied widely between samples. A 17β-HSD type 1 inhibition pattern was observed in 23% of the samples and a type 2 pattern in 25%. E 2 formation from estrone sulfate (E 1 S) was detected in 98% (47/48) of the samples. 17β-HSD type 1, type 2 and type 5 mRNA was detected in matched primary tumor and metastases. Evaluation of 17β-HSD and sulfatase activity levels, activity ratios and inhibition patterns may help predict tumor response to endocrine therapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 51-58 |
| Number of pages | 8 |
| Journal | Molecular and Cellular Endocrinology |
| Volume | 301 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Mar 25 2009 |
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Keywords
- 17β-Hydroxysteroid dehydrogenase
- 3α-Hydroxysteroid dehydrogenase
- 3β-Hydroxysteroid dehydrogenase
- Estrone sulfatase
- Ovarian cancer
- Steroid metabolism
Cite this
Steroid-converting enzymes in human ovarian carcinomas. / Chura, Justin C.; Ryu, Hyung S.; Simard, Marc; Poirier, Donald; Tremblay, Yves; Brooker, Doris C.; Blomquist, Charles H.; Argenta, Peter A.
In: Molecular and Cellular Endocrinology, Vol. 301, No. 1-2, 25.03.2009, p. 51-58.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Steroid-converting enzymes in human ovarian carcinomas
AU - Chura, Justin C.
AU - Ryu, Hyung S.
AU - Simard, Marc
AU - Poirier, Donald
AU - Tremblay, Yves
AU - Brooker, Doris C.
AU - Blomquist, Charles H.
AU - Argenta, Peter A
PY - 2009/3/25
Y1 - 2009/3/25
N2 - Anti-estrogen therapies for treating ovarian carcinoma have had mixed outcomes suggesting some tumors may be estrogen-dependent. We assayed the activity levels of 17β-hydroxysteroid dehydrogenase (17β-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), 3α-hydroxysteroid dehydrogenase (3α-HSD/3-KSR) and estrone sulfatase in a series of ovarian epithelial carcinomas. 17β-HSD activity ratios with estradiol (E 2 ) and testosterone (T), and inhibition by isoform-specific inhibitors were used to estimate the contributions of 17β-HSD isoforms. Activity levels were highest for estrone sulfatase, followed, respectively by 17β-HSD, 3α-HSD/3-KSR, and 3β-HSD. E 2 /T activity ratios varied widely between samples. A 17β-HSD type 1 inhibition pattern was observed in 23% of the samples and a type 2 pattern in 25%. E 2 formation from estrone sulfate (E 1 S) was detected in 98% (47/48) of the samples. 17β-HSD type 1, type 2 and type 5 mRNA was detected in matched primary tumor and metastases. Evaluation of 17β-HSD and sulfatase activity levels, activity ratios and inhibition patterns may help predict tumor response to endocrine therapy.
AB - Anti-estrogen therapies for treating ovarian carcinoma have had mixed outcomes suggesting some tumors may be estrogen-dependent. We assayed the activity levels of 17β-hydroxysteroid dehydrogenase (17β-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), 3α-hydroxysteroid dehydrogenase (3α-HSD/3-KSR) and estrone sulfatase in a series of ovarian epithelial carcinomas. 17β-HSD activity ratios with estradiol (E 2 ) and testosterone (T), and inhibition by isoform-specific inhibitors were used to estimate the contributions of 17β-HSD isoforms. Activity levels were highest for estrone sulfatase, followed, respectively by 17β-HSD, 3α-HSD/3-KSR, and 3β-HSD. E 2 /T activity ratios varied widely between samples. A 17β-HSD type 1 inhibition pattern was observed in 23% of the samples and a type 2 pattern in 25%. E 2 formation from estrone sulfate (E 1 S) was detected in 98% (47/48) of the samples. 17β-HSD type 1, type 2 and type 5 mRNA was detected in matched primary tumor and metastases. Evaluation of 17β-HSD and sulfatase activity levels, activity ratios and inhibition patterns may help predict tumor response to endocrine therapy.
KW - 17β-Hydroxysteroid dehydrogenase
KW - 3α-Hydroxysteroid dehydrogenase
KW - 3β-Hydroxysteroid dehydrogenase
KW - Estrone sulfatase
KW - Ovarian cancer
KW - Steroid metabolism
UR - http://www.scopus.com/inward/record.url?scp=60249091167&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=60249091167&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2008.07.015
DO - 10.1016/j.mce.2008.07.015
M3 - Article
C2 - 18723074
AN - SCOPUS:60249091167
VL - 301
SP - 51
EP - 58
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 1-2
ER -